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Keywords = gentamicin nephrotoxicity

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18 pages, 3990 KiB  
Article
Hypovitaminosis D Does Not Aggravate the Progression of Gentamicin-Induced Kidney Injury in Rats
by Ana Lívia D. Maciel, Amanda L. Deluque, Beatriz M. Oliveira, Cláudia S. Souza, Heloísa D. C. Francescato, Cleonice Giovanini, Francisco J. A. de Paula, Terezila M. Coimbra and Rildo A. Volpini
Diseases 2025, 13(7), 200; https://doi.org/10.3390/diseases13070200 - 28 Jun 2025
Viewed by 297
Abstract
Background/Objectives: Gentamicin is one of the most effective and widely used antibiotics to treat serious infections. In addition to its bactericidal properties, gentamicin has a nephrotoxic effect that results in acute kidney injury (AKI). AKI may be intensified by hypovitaminosis D. This [...] Read more.
Background/Objectives: Gentamicin is one of the most effective and widely used antibiotics to treat serious infections. In addition to its bactericidal properties, gentamicin has a nephrotoxic effect that results in acute kidney injury (AKI). AKI may be intensified by hypovitaminosis D. This study evaluated the effect of hypovitaminosis D in the progression of gentamicin-induced renal injury. Methods: Male Wistar Hannover rats received a standard (SD) or a vitamin D-free diet (VitD) before gentamicin treatment. After that, we divided the animals into four groups: Ctrl VitD, SD diet, and saline injection; Ctrl VitD, VitD diet, and saline injection; Genta VitD, SD diet, and gentamicin injection (40 mg/kg; IM); Genta VitD, VitD diet, and gentamicin injection (40 mg/kg; IM). After the end of gentamicin treatment, we followed the animals for 5 days (protocol 1) and 30 days (protocol 2). Results: The Genta VitD group (protocol 1) presented impaired renal function. Regarding morphological analyses, the Genta VitD group presented necrotic tubules (protocol 1) and atrophied tubules (protocol 2). In the inflammatory scenario, the Genta VitD group presented an increase in the number of CD68+ cells, as well as in the levels of interleukin 1β (protocols 1 and 2). In addition, gentamicin-treated animals (protocols 1 and 2) presented an increased renal expression of vimentin and fibronectin. Despite the notable changes in functional, inflammatory, and structural parameters induced by gentamicin, hypovitaminosis D did not aggravate the renal injury in this experimental model. Conclusion: Hypovitaminosis D did not aggravate the progression of gentamicin-induced renal injury in rats. Full article
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14 pages, 1761 KiB  
Article
Ergosterol Protects Canine MDCK Cells from Gentamicin-Induced Damage by Modulating Autophagy and Apoptosis
by Zhipeng Qin, Liuwei Xie, Yao Wang, Na Zhang, Hailong Bi, Mingqiang Song and Chao Xu
Metabolites 2025, 15(6), 373; https://doi.org/10.3390/metabo15060373 - 5 Jun 2025
Viewed by 489
Abstract
Background: Renal injury is a critical health issue in pet dogs, often exacerbated by drug-induced nephrotoxicity such as gentamicin (GM). This study investigated the protective effects of ergosterol (Erg), a natural compound from edible mushrooms, against GM-induced damage in Madin–Darby canine kidney (MDCK) [...] Read more.
Background: Renal injury is a critical health issue in pet dogs, often exacerbated by drug-induced nephrotoxicity such as gentamicin (GM). This study investigated the protective effects of ergosterol (Erg), a natural compound from edible mushrooms, against GM-induced damage in Madin–Darby canine kidney (MDCK) cells. Methods: MDCK cells were treated with GM (0.5–3 mmol/L) for 12 h to establish injury. Erg (1 to 32 μg/mL) was pretreated for 12 h before GM exposure (2 mmol/L). Cell viability, nitric oxide (NO), lactate dehydrogenase (LDH), oxidative stress markers (SOD, GSH, CAT, MDA), inflammatory cytokines (IL-1β, IL-6, TNF-α), renal function indicators (Scr, BUN), and autophagy/apoptosis-related proteins (ATG5, Beclin1, P62, BAX, BCL-2) were assessed via CCK-8, ELISA, fluorescence staining, and Western blot. Statistical significance (p < 0.05) was determined by ANOVA and LSD post hoc tests. Results: GM (2 mmol/L) significantly reduced cell viability (p < 0.01) and elevated NO and LDH levels (p < 0.01). Erg pretreatment (4–8 μg/mL) restored cell viability (p < 0.01), suppressed NO (p < 0.01) and LDH release (p < 0.01), and enhanced antioxidant enzyme activities (SOD, GSH, CAT; p < 0.01). Erg attenuated GM-induced reactive oxygen species (ROS) overproduction (p < 0.01) and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.01). Renal markers Scr and BUN were reduced (p < 0.01). Mechanistically, Erg upregulated autophagy proteins ATG5 and Beclin1 (p < 0.01), reduced P62 accumulation (p < 0.01), and lowered the BAX/BCL-2 ratio (p < 0.01). Conclusions: Erg protects MDCK cells from GM-induced nephrotoxicity by restoring autophagy flux, suppressing mitochondrial apoptosis, and mitigating oxidative stress and inflammation. These findings highlight Erg’s potential as a natural therapeutic agent for canine renal injury. Further in vivo studies are needed to validate its clinical efficacy. Full article
(This article belongs to the Special Issue Effects of Nutrition Intake on Pet Metabolism)
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10 pages, 234 KiB  
Article
Incidence of PJI in Total Knee Arthroplasty Patients Following Expanded Gram-Negative Antibiotic Prophylactic Protocol
by Anzar Sarfraz, Cameron Bussey-Sutton, Emily M. Ronan, Farouk Khury, Joseph A. Bosco, Ran Schwarzkopf and Vinay K. Aggarwal
Microorganisms 2025, 13(5), 1002; https://doi.org/10.3390/microorganisms13051002 - 27 Apr 2025
Viewed by 493
Abstract
The efficacy of “Expanded Gram-Negative Antimicrobial Prophylaxis” (EGNAP) in preventing postoperative infections has been previously reported in total hip arthroplasty (THA). However, it remains unclear as to whether these benefits extend to total knee arthroplasty (TKA). This study investigated whether adding EGNAP to [...] Read more.
The efficacy of “Expanded Gram-Negative Antimicrobial Prophylaxis” (EGNAP) in preventing postoperative infections has been previously reported in total hip arthroplasty (THA). However, it remains unclear as to whether these benefits extend to total knee arthroplasty (TKA). This study investigated whether adding EGNAP to our institution’s preoperative antibiotic prophylaxis protocol would affect periprosthetic joint infection (PJI) risk in TKA patients. We retrospectively reviewed 10,666 elective, unilateral, primary TKA cases performed at a single-specialty tertiary academic hospital from 2018 to 2022. Before June 2021, all patients received 2 g of cefazolin for 24 h as part of the prophylactic antibiotic protocol. After June 2021, gentamicin or aztreonam (EGNAP) was added to the protocol for all TKA patients. Patients were grouped based on whether they received EGNAP or not (control group) before surgery. The groups were propensity score-matched in a 2:1 ratio. PJI and nephrotoxicity (using RIFLE criteria) risk was compared. After matching, the final study population consisted of 3007 patients in the non-EGNAP group and 1503 patients in the EGNAP group. There was no significant difference between the EGNAP and no EGNAP groups in the overall incidence of PJI (1.9% vs. 2.0%; p = 0.111) or the incidence of Gram-positive PJIs (0.3% vs. 0.8%; p = 0.103). The incidence of Gram-negative PJIs was 0.5% in the EGNAP group and 0.4% in the no EGNAP group, which was also not different between the groups (p = 0.692). There were no differences in nephrotoxicity between groups (p = 0.521). The addition of EGNAP to the antibiotic prophylactic protocol prior to TKA had no effect on overall or Gram-negative PJI risk in TKA patients. The findings of this study suggest that while EGNAP is safe to use and has minimal nephrotoxic effects, its prophylactic benefits do not extend to the primary TKA population. This may be attributed to the generally low rate of Gram-negative infections in TKA patients, where adding EGNAP does not provide a clear advantage in reducing the risk of such infections, unlike its potential benefits in primary THA population. This study investigates the effects of using prophylactic Gram-negative antibiotics prior to TKA and shows that though it is safe to use, Gram-negative bacterial coverage may have no impact on postoperative infection incidence. Full article
(This article belongs to the Collection Device-Related Infections and Bacterial Biofilms)
19 pages, 6773 KiB  
Article
Evaluation of Single and Multi-Strain Probiotics with Gentamicin Against E. coli O157:H7: Insights from In Vitro and In Vivo Studies
by Fatima H. Fneish, Khaled H. Abd El Galil and Souraya A. Domiati
Microorganisms 2025, 13(2), 460; https://doi.org/10.3390/microorganisms13020460 - 19 Feb 2025
Cited by 1 | Viewed by 1514
Abstract
The emergence of antibiotic-resistant food-borne pathogens, especially Escherichia coli O157:H7, highlights the urgent need for innovative treatment strategies, particularly in light of rising resistances and the ongoing controversy surrounding antibiotic use in response to E. coli O157:H7 infections. To address this issue, we [...] Read more.
The emergence of antibiotic-resistant food-borne pathogens, especially Escherichia coli O157:H7, highlights the urgent need for innovative treatment strategies, particularly in light of rising resistances and the ongoing controversy surrounding antibiotic use in response to E. coli O157:H7 infections. To address this issue, we explored the potential of single- and multi-strain probiotics, both independently and in combination with gentamicin, through a series of in vitro and in vivo experiments. In vitro, gentamicin alone produced a mean inhibition zone of 12.9 ± 2.27 mm against E. coli O157:H7. The combination of gentamicin with single-strain probiotics (P1) increased the inhibition zone to 16.5 ± 2.24 mm (p < 0.05), while the combination with multi-strain probiotics (P2) resulted in the largest inhibition zone of 19 ± 2.8 mm (p < 0.05). In vivo, mice infected with E. coli O157:H7 and treated with P2, gentamicin (G), or their combination (G+P2), achieved 100% survival, no pathological symptoms, and full weight recovery within seven days. Conversely, mice treated with P1 or G+P1 exhibited lower survival rates (71.4% and 85%, respectively) and slower weight recovery. Hematological parameters improved across all groups, but kidney function analysis showed significantly higher serum creatinine levels in the P1, G, G+P1, and G+P2 groups compared to the P2 group (P1: 0.63 ± 0.15 mg/dL; G: 0.34 ± 0.09 mg/dL; G+P1: 0.53 ± 0.19 mg/dL; G+P2: 0.5 ± 0.23 mg/dL vs. P2: 0.24 ± 0.2 mg/dL). Histological analysis showed better intestinal and kidney tissue recovery in the P2 group, while the P1 and G+P1 groups exhibited abnormal ileal structures and severe cortical bleeding. These findings highlight the promise of multi-strain probiotics, alone or in conjunction with antibiotics, as a therapeutic strategy for E. coli O157:H7 infections. However, the nephrotoxicity associated with gentamicin co-administration remains a limitation, warranting further studies to optimize this approach. Full article
(This article belongs to the Section Antimicrobial Agents and Resistance)
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14 pages, 1561 KiB  
Article
Chrysin Attenuates Gentamicin-Induced Renal Injury in Rats Through Modulation of Oxidative Damage and Inflammation via Regulation of Nrf2/AKT and NF-kB/KIM-1 Pathways
by Talat A. Albukhari, Rehab M. Bagadood, Bayan T. Bokhari, Waheed A. Filimban, Hatem Sembawa, Nani Nasreldin, Hossam E. Gadalla and Mohamed E. El-Boshy
Biomedicines 2025, 13(2), 271; https://doi.org/10.3390/biomedicines13020271 - 23 Jan 2025
Cited by 2 | Viewed by 1637
Abstract
Background: Gentamicin (GM) is extensively used as an antibiotic for the treatment of infections caused by Gram-negative bacteria. Oxidative stress and proinflammatory cytokines are implicated in GM-induced renal damage. Chrysin (CH), also known as 5,7-dihydroxyflavone, has been used in traditional medicine to treat [...] Read more.
Background: Gentamicin (GM) is extensively used as an antibiotic for the treatment of infections caused by Gram-negative bacteria. Oxidative stress and proinflammatory cytokines are implicated in GM-induced renal damage. Chrysin (CH), also known as 5,7-dihydroxyflavone, has been used in traditional medicine to treat various kidney disorders. The aim of this study was to investigate the antioxidant, anti-apoptotic, and anti-inflammatory effects of CH against nephrotoxicity induced by GM. Methods: Male rats were separated into four equal groups: a negative control group (NC), a CH-treated group (100 mg/kg/day per os), a group treated with GM (100 mg/kg/day IM), and a group treated with both GM and CH (100 mg/kg/day), for 10 days. Blood and urine renal markers were investigated. Results: GM caused increases in the serum creatinine and urea levels and decreases in creatinine clearance, urine flow, and urine volume in the GM-treated rats. Moreover, there were increases in the levels of IL-1β, TNF-α, IL-18, and MDA in the renal tissues, with an augmented expression of NF-κB/KIM-1, as well as decreases in antioxidant marker (GSH, GPx, CAT, and SOD) activities and decreased expressions of the anti-inflammatory transcription factors Nrf2 and AKT. The simultaneous treatment with CH in the GM-treated group protected renal tissues against the nephrotoxicity induced by GM, as demonstrated by the normalization of renal markers and improvement in histopathological damage. Conclusions: This study reveals that CH may attenuate GM-induced renal toxicity in rats. Full article
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26 pages, 10278 KiB  
Article
Sambucus nigra-Lyophilized Fruit Extract Attenuated Acute Redox–Homeostatic Imbalance via Mutagenic and Oxidative Stress Modulation in Mice Model on Gentamicin-Induced Nephrotoxicity
by Kamelia Petkova-Parlapanska, Ivaylo Stefanov, Julian Ananiev, Tsvetelin Georgiev, Petya Hadzhibozheva, Veselina Petrova-Tacheva, Nikolay Kaloyanov, Ekaterina Georgieva, Galina Nikolova and Yanka Karamalakova
Pharmaceuticals 2025, 18(1), 85; https://doi.org/10.3390/ph18010085 - 13 Jan 2025
Viewed by 1532
Abstract
Background: Gentamicin (GM) administration is associated with decreased metabolism, increased oxidative stress, and induction of nephrotoxicity. Sambucus nigra L., containing flavonoids, anthocyanins, and phytosterols, possesses antioxidant and anti-inflammatory potential. Objectives: The present study aimed to investigate the nephroprotective and anti-inflammatory potential of lyophilized [...] Read more.
Background: Gentamicin (GM) administration is associated with decreased metabolism, increased oxidative stress, and induction of nephrotoxicity. Sambucus nigra L., containing flavonoids, anthocyanins, and phytosterols, possesses antioxidant and anti-inflammatory potential. Objectives: The present study aimed to investigate the nephroprotective and anti-inflammatory potential of lyophilized Sambucus nigra fruit extract (S. nigra extract) to reduce acute oxidative stress and residual toxicity of GM in a 7-day experimental model in Balb/c rodents. Methods: The S. nigra extract was lyophilized (300 rpm; 10 min; −45 °C) to improve pharmacological properties. Balb/c mice were divided into four (n = 6) groups: controls; S. nigra extract per os (120 mg kg−1 day−1 bw); GM (200 mg kg−1 day−1 bw) (4); and GM + S. nigra therapy. The activities of antioxidant and renal enzymes, cytokines, and levels of oxidative stress biomarkers—Hydroxiproline, CysC, GST, KIM-1, PGC-1α, MDA, GSPx—were analyzed by ELISA tests. The ROS and RNS levels, as well as 5-MSL-protein oxidation, were measured by EPR spectroscopy. Results: The antioxidant-protective effect of S. nigra extract (120 mg kg−1) was demonstrated by reduced MDA, ROS, and RNS and increased activation of endogenous enzymes. Furthermore, S. nigra extract significantly reduced the expression of IL-1β, IL-6, IL-10, TNF-α, IFN-γ, and KIM-1 and regulated collagen/protein (PGC-1α and albumin) deposition in renal tissues. Conclusions: Histological evaluation confirmed that S. nigra (120 mg kg−1) attenuated renal dysfunction and structural damage by modulating oxidative stress and acute inflammation and could be used as an anti-fibrotic alternative in GM nephrotoxicity. Full article
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16 pages, 2299 KiB  
Article
Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles as Natural Nanocarriers in the Treatment of Nephrotoxic Injury In Vitro
by Márcia Bastos Convento, Andreia Silva de Oliveira, Mirian Aparecida Boim and Fernanda Teixeira Borges
Cells 2024, 13(19), 1658; https://doi.org/10.3390/cells13191658 - 7 Oct 2024
Cited by 1 | Viewed by 3548
Abstract
Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and [...] Read more.
Umbilical cord mesenchymal stem cell-derived extracellular vesicles (UC-EVs) are valuable in nanomedicine as natural nanocarriers, carrying information molecules from their parent cells and fusing with targeted cells. miRNA-126, specific to endothelial cells and derived from these vesicles, supports vascular integrity and angiogenesis and has protective effects in kidney diseases. Objective: This study investigates the delivery of miRNA-126 and anti-miRNA-126 via UC-EVs as natural nanocarriers for treating nephrotoxic injury in vitro. Method: The umbilical cord-derived mesenchymal stem cell and UC-EVs were characterized according to specific guidelines. Rat kidney proximal tubular epithelial cells (tubular cells) were exposed to nephrotoxic injury through of gentamicin and simultaneously treated with UC-EVs carrying miRNA-126 or anti-miRNA-126. Specific molecules that manage cell cycle progression, proliferation cell assays, and newly synthesized DNA and DNA damage markers were evaluated. Results: We observed significant increases in the expression of cell cycle markers, including PCNA, p53, and p21, indicating a positive cell cycle regulation with newly synthesized DNA via BrDU. The treatments reduced the expression of DNA damage marker, such as H2Ax, suggesting a lower rate of cellular damage. Conclusions: The UC-EVs, acting as natural nanocarriers of miRNA-126 and anti-miRNA-126, offer nephroprotective effects in vitro. Additionally, other components in UC-EVs, such as proteins, lipids, and various RNAs, might also contribute to these effects. Full article
(This article belongs to the Section Stem Cells)
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15 pages, 1424 KiB  
Article
Confirming the Suitability of a Gentamicin Dosing Strategy in Neonates Using the Population Pharmacokinetic Approach with Truncated Sampling Duration
by Bonifasius Siyuka Singu, Roger Karel Verbeeck, Clarissa Hildegard Pieper and Ene I. Ette
Children 2024, 11(8), 898; https://doi.org/10.3390/children11080898 - 26 Jul 2024
Viewed by 1808
Abstract
(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This [...] Read more.
(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This was a prospective, observational study conducted in Namibia with 52 neonates. A dose of 5 mg/kg gentamicin was administered over 3–5 s every 24 h in combination with benzylpenicillin 100,000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Two blood samples were collected from each participant using a truncated pharmacokinetic sampling schedule. (3) Results: The one-compartment linear pharmacokinetic model best described the data. Birthweight, postnatal age, and white blood cell count were predictive of clearance (CL), while birthweight was predictive of volume (V). For the typical neonate (median weight 1.57 kg, median postnatal age 4 days (0.011 years), median log-transformed WBC of 2.39), predicted CL and V were 0.069 L/h and 0.417 L, respectively—similar to literature values. Simulated gentamicin concentrations varied with respect to postnatal age and bodyweight. (4) Conclusions: A 5 mg/kg/24 h dosage regimen yielded simulated gentamicin concentrations with respect to age and birthweight similar to those previously reported in the literature to be safe and efficacious, confirming its appropriateness. Full article
(This article belongs to the Special Issue Neonatal Clinical Pharmacology)
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11 pages, 664 KiB  
Case Report
An Aminoglycoside-Sparing Regimen with Double Beta-Lactam to Successfully Treat Granulicatella adiacens Prosthetic Aortic Valve Endocarditis—Time to Change Paradigm?
by Alberto Pagotto, Floriana Campanile, Paola Conti, Francesca Prataviera, Paola Della Siega, Sarah Flammini, Simone Giuliano, Luca Martini, Davide Pecori, Assunta Sartor, Maria Screm, Tosca Semenzin and Carlo Tascini
Infect. Dis. Rep. 2024, 16(2), 249-259; https://doi.org/10.3390/idr16020020 - 14 Mar 2024
Cited by 1 | Viewed by 2775
Abstract
(1) Background: Granulicatella adiacens is a former nutritionally variant streptococci (NVS). NVS infective endocarditis (IE) is generally characterized by a higher rate of morbidity and mortality, partially due to difficulties in choosing the most adequate microbiological culture method and the most effective treatment [...] Read more.
(1) Background: Granulicatella adiacens is a former nutritionally variant streptococci (NVS). NVS infective endocarditis (IE) is generally characterized by a higher rate of morbidity and mortality, partially due to difficulties in choosing the most adequate microbiological culture method and the most effective treatment strategy, and partially due to higher rates of complications, such as heart failure, peripheral septic embolism, and peri-valvular abscess, as well as a higher rate of valve replacement. Depending on the affected valve (native valve endocarditisNVE, or prosthetic valve endocarditisPVE), the American Heart Association (AHA) 2015 treatment guidelines (GLs) suggest penicillin G, ampicillin, or ceftriaxone plus gentamicin (2 weeks for NVE and up to 6 weeks for PVE), while vancomycin alone may be a reasonable alternative in patients who are intolerant of β-lactam therapy. The European Society of Cardiology (ESC) 2023 GLs recommend treating NVE with penicillin G, ceftriaxone, or vancomycin for 6 weeks, suggesting combined with an aminoglycoside (AG) for at least the first 2 weeks only for PVE; likewise, the same recommendations for IE due to Enterococcus faecalis. (2) Methods: Starting from the case of a 51-year-old man with G. adiacens aortic bio-prosthesis IE who was successfully treated with aortic valve replacement combined with double beta-lactams, an AG-sparing regimen, we performed microbiology tests in order to validate this potential treatment change. (3) Results: As for E. faecalis IE, we found that the combination of ampicillin plus cephalosporines (like ceftriaxone or ceftobiprole) showed a synergistic effect in vitro, probably due to wider binding to penicillin-binding proteins (PBPs), thus contributing to enhanced bacterial killing and good clinical outcome, as well as avoiding the risk of nephrotoxicity due to AG association therapy. (4) Conclusions: Further studies are required to confirm this hypothesis, but double beta-lactams and an adequate sourcecontrol could be a choice in treating G. adiacens IE. Full article
(This article belongs to the Section Bacterial Diseases)
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22 pages, 5351 KiB  
Article
LC/MS-Based Profiling of Hedyotis aspera Whole-Plant Methanolic Extract and Evaluation of Its Nephroprotective Potential against Gentamicin-Induced Nephrotoxicity in Rats Supported by In Silico Studies
by Dsnbk Prasanth, Lingareddygari Siva Sanker Reddy, Tharani Dasari, Pamula Reddy Bhavanam, Sheikh F. Ahmad, Rahul Nalluri and Praveen Kumar Pasala
Separations 2023, 10(11), 552; https://doi.org/10.3390/separations10110552 - 30 Oct 2023
Cited by 5 | Viewed by 2991
Abstract
Many high-altitude plants, such as Hedyotis aspera, need to be explored for their possible medicinal value. The current study explored the protective effect of Hedyotis aspera methanolic extract whole plant (HAME) against gentamicin-induced nephrotoxicity in rats. It profiled their phytocontents using HPLC-QTOF-MS/MS [...] Read more.
Many high-altitude plants, such as Hedyotis aspera, need to be explored for their possible medicinal value. The current study explored the protective effect of Hedyotis aspera methanolic extract whole plant (HAME) against gentamicin-induced nephrotoxicity in rats. It profiled their phytocontents using HPLC-QTOF-MS/MS analytic methods. The LC-MS analysis of HAME revealed 27 compounds. Eight compounds followed Lipinski’s rule of five and were found to be potential TNF-α inhibitors with binding affinities of −6.9, −6.3, −6.3, and −6.3 Kcal/mol, such as 14,19-Dihydroaspidospermatine, coumeroic acid, lycocernuine and muzanzagenin. All potential compounds were found to be safe according to the ADMET analysis. The in vitro 2,2-diphenyl-1-picrlhydrazyl (DPPH) assay assessed the antioxidant activity. The nephroprotective activity was assessed in rats using a gentamicin-induced nephrotoxicity model. The in vivo analysis involved histological examination, tissue biochemical evaluation, including a kidney function test, catalase activity (CAT), reduced glutathione (GSH) levels, superoxide dismutase (SOD), and the inflammatory mediator TNF-α. Based on DPPH activity, HAME showed a scavenging activity IC50 of 264.8 ± 1.2 µg/mL, while results were compared with a standard vitamin C IC50 of 45 ± 0.45 µg/mL. Nephrotoxicity was successfully induced, as shown by elevated creatinine and uric acid levels, decreased kidney antioxidant levels, and increased TNF-α in gentamicin-treated rats. The HAME treatment significantly reduced serum creatinine and uric acid levels, increased GSH (p < 0.01 **), CAT (p < 0.01 **), and SOD (p < 0.001 ***), and decreased TNF-α (p < 0.001 ***) in nephrotoxic rats. The histopathological examination of the groups treated with HAME revealed a notable enhancement in the structural integrity of the kidneys as compared to the group exposed to gentamicin. Biochemical, histopathological, and phytochemical screening of HAME suggests that it has nephroprotective potential, owing to the presence of 14,19-Dihydroaspidospermatine, coumeroic acid, lycopene, and muzanzagenin. Full article
(This article belongs to the Special Issue Advanced Research on Extraction and Analysis of Plant Extracts)
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28 pages, 14717 KiB  
Article
The Nephroprotective Effect of Cornelian Cherry (Cornus mas L.) and Rowanberry (Sorbus aucuparia L.) in Gentamicin-Induced Nephrotoxicity on Wistar Rats with Emphasis on the Evaluation of Novel Renal Biomarkers and the Antioxidant Capacity in Correlation with Nitro-Oxidative Stress
by Mara Aurori, Sanda Andrei, Alexandra Iulia Dreanca, Andreea Georgiana Morohoschi, Mihaela Cotul, Mihaela Niculae, Monica Irina Nan, Andrei Răzvan Codea and Adrian Florin Gal
Nutrients 2023, 15(20), 4392; https://doi.org/10.3390/nu15204392 - 16 Oct 2023
Cited by 9 | Viewed by 2500
Abstract
In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce [...] Read more.
In spite of its well-known nephrotoxicity, gentamicin is nonetheless routinely used in humans and animals. However, no adjuvant treatments have been implemented to mitigate this harmful effect. Given this concern, medicinal plants represent a significant reservoir of natural antioxidants that could potentially reduce the renal oxidative stress induced by gentamicin. Therefore, the main objective of this research was to investigate the nephroprotective properties of Cornus mas and Sorbus aucuparia fruits in an experimental model of nephrotoxicity. The 3-week study was performed on male Wistar rats, which were randomly divided into six experimental groups, being subcutaneously treated with 50 mg/kg gentamicin and orally given Cornus mas and Sorbus aucuparia extracts, in doses of 40 mg/kg and 10 mg/kg, respectively. Antioxidant therapy significantly improved the nitro-oxidative stress parameters as well as the specific renal biomarkers KIM-1 and iNAG, demonstrating a considerable renal tubular protective impact. These outcomes were reinforced by biochemical and histopathological enhancements. Nevertheless, neither of the tested extracts succeeded in substantially diminishing BUN levels. Additionally, CysC did not significantly decline following extracts treatment, suggesting that the remedies did not effectively protect renal glomeruli against gentamicin stress. Future studies are required in order to determine the underlying mechanisms of these berries. Full article
(This article belongs to the Special Issue Oxidative Stress and Protective Effects of Natural Products in Health)
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18 pages, 4366 KiB  
Article
Vitamin E and Silymarin Reduce Oxidative Tissue Damage during Gentamycin-Induced Nephrotoxicity
by Tsvetelin Georgiev, Galina Nikolova, Viktoriya Dyakova, Yanka Karamalakova, Ekaterina Georgieva, Julian Ananiev, Veselin Ivanov and Petya Hadzhibozheva
Pharmaceuticals 2023, 16(10), 1365; https://doi.org/10.3390/ph16101365 - 27 Sep 2023
Cited by 10 | Viewed by 2116
Abstract
Aminoglycoside antibiotics and gentamicin (GN), in particular, are still widely used in clinical practice. It is a well-known fact that GN causes nephrotoxicity, and redox disturbances are discussed as a factor in its side effects. Recently, a new type of cell oxidative death, [...] Read more.
Aminoglycoside antibiotics and gentamicin (GN), in particular, are still widely used in clinical practice. It is a well-known fact that GN causes nephrotoxicity, and redox disturbances are discussed as a factor in its side effects. Recently, a new type of cell oxidative death, named ferroptosis, was discovered; it is associated with iron accumulation in the cell, glutathione (GSH) depletion and inactivation of glutathione peroxidase-4 (GPX4), reactive oxygen species (ROS) increment with concomitant lipid peroxidation. In this regard, a possible connection between GN-induced renal damage, ferroptosis and the overall antioxidant status of the organism could be investigated. Moreover, due to its beneficial effects, GN is still one of the main choices as a therapeutic agent for several diseases, and the possible reduction of its side effects with the application of certain antioxidants will be of important clinical significance. The study was conducted with adult male white mice divided into several groups (n = 6). GN nephrotoxicity was induced by the administration of GN 100–200 mg/kg i.p. for 10 days. The control group received only saline. The other groups received either Vitamin E (400 mg/kg p.o.) or Silymarin (200 mg/kg p.o.) applied alone or together with GN for the same period. After the end of the study, the animals were sacrificed, and blood and tissue samples were taken for the assessment of biochemical parameters and antioxidant status, as well as routine and specific for GPX4 histochemistry examination. The experimental results indicate that GN-induced nephrotoxicity negatively modulates GPX4 activity and is associated with increased production of ROS and lipid peroxidation. The groups treated with antioxidants demonstrated preserved antioxidant status and better GPX4 activity. In conclusion, the inhibition of ROS production and especially the suppression of ferroptosis, could be of clinical potential and can be applied as a means of reducing the toxic effects of GN application. Full article
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19 pages, 4248 KiB  
Article
Efficacy and Safety of Antibiotic Impregnated Microporous Nanohydroxyapatite Beads for Chronic Osteomyelitis Treatment: A Multicenter, Open-Label, Prospective Cohort Study
by Chittawee Jiamton, Adinun Apivatgaroon, Saree Aunaramwat, Banchai Chawalitrujiwong, Chaiwat Chuaychoosakoon, Sitthiphong Suwannaphisit, Choen Jirawison, Chonlathan Iamsumang, Pinkawas Kongmalai, Pawaris Sukvanich, Pongtep Na Nakorn, Worawit Ongbumrungphan, Pawin Rattanasumrit, Suthee Tharakulphan, Thanachai Thongtanworapat, Faungchat Thammarakcharoen, Autcharaporn Srion, Jintamai Suwanprateeb and Bancha Chernchujit
Antibiotics 2023, 12(6), 1049; https://doi.org/10.3390/antibiotics12061049 - 15 Jun 2023
Cited by 7 | Viewed by 4511
Abstract
Chronic osteomyelitis is still a serious health problem that causes disabling conditions and has an impact on the quality of life. The objective of this study was to determine the clinical efficacy and safety of localized antibiotics delivery via impregnated microporous nanohydroxyapatite (nHA-ATB) [...] Read more.
Chronic osteomyelitis is still a serious health problem that causes disabling conditions and has an impact on the quality of life. The objective of this study was to determine the clinical efficacy and safety of localized antibiotics delivery via impregnated microporous nanohydroxyapatite (nHA-ATB) beads for chronic osteomyelitis treatment. A total of 62 patients were enrolled in this study. After radical surgical debridement, the bone defect was filled with three types of antibiotics (vancomycin or gentamicin or fosfomycin) impregnated HA beads. The follow-up period was 48 weeks. It was found that the success rate was approximately 98% with a re-infection in only one patient. Quality of life of all patients after treatment improved significantly over time. Systemic exposure to vancomycin and gentamicin after beads implantation was limited and high local antibiotics concentrations were found in wound drainage fluid at 24, 48 and 72 h. Blood biochemistry measurements did not show any nephrotoxic or hepatotoxic effects. 20 adverse events were reported, but 90% of the events were resolved without having to remove the beads and the patients recovered. Satisfactory outcomes were observed in terms of success rate, quality of life and adverse effect. nHA-ATB beads impregnated by vancomycin or gentamicin or fosfomycin could potentially be employed as an alternative product of choice for localized antibiotics delivery in chronic osteomyelitis treatment. Full article
(This article belongs to the Special Issue Advances in Orthopedic Infection Management and Antibiotic Treatment)
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13 pages, 1043 KiB  
Article
Preliminary Investigation of Side Effects of Polymyxin B Administration in Hospitalized Horses
by Julia N. van Spijk, Katrin Beckmann, Meret Wehrli Eser, Martina Stirn, Andrea E. Steuer, Lanja Saleh and Angelika Schoster
Antibiotics 2023, 12(5), 854; https://doi.org/10.3390/antibiotics12050854 - 5 May 2023
Cited by 2 | Viewed by 2255
Abstract
Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed [...] Read more.
Neuro- and nephrotoxicity of polymyxins are known but clinical studies in horses are lacking. The aim of this study was to describe neurogenic and nephrogenic side effects of hospitalized horses receiving Polymyxin B (PolyB) as part of their treatment plan. Twenty horses diagnosed with surgical colic (n = 11), peritonitis (n = 5), typhlocolitis (n = 2), pneumonia, and pyometra (each n = 1) were included. Antimicrobial treatment was randomized to GENTA (gentamicin 10 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV) or NO GENTA (marbofloxacin 2 mg/kg bwt q24 h IV, penicillin 30.000 IU/kg q6 h IV). The duration of PolyB treatment ranged from 1 to 4 days. Clinical and neurological examinations were performed, and serum PolyB concentrations were measured daily during and three days following PolyB treatment. Urinary analysis, plasma creatinine, urea and SDMA were assessed every other day. Video recordings of neurological examinations were graded by three blinded observers. All horses showed ataxia during PolyB treatment in both groups (median maximum ataxia score of 3/5, range 1–3/5). Weakness was detected in 15/20 (75%) horses. In 8/14 horses, the urinary γ-glutamyltransferase (GGT)/creatinine ratio was elevated. Plasma creatinine was mildly elevated in 1/16 horses, and SDMA in 2/10 horses. Mixed-model analysis showed a significant effect of time since last PolyB dose (p = 0.0001, proportional odds: 0.94) on the ataxia score. Ataxia and weakness should be considered as reversible adverse effects in hospitalized horses receiving PolyB. Signs of tubular damage occurred in a considerable number of horses; therefore, the nephrotoxic effect of polymyxins should be considered and urinary function monitored. Full article
(This article belongs to the Section Antibiotics in Animal Health)
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20 pages, 10295 KiB  
Article
Parthenolide Phytosomes Attenuated Gentamicin-Induced Nephrotoxicity in Rats via Activation of Sirt-1, Nrf2, OH-1, and NQO1 Axis
by Rawan S. Albalawi, Lenah S. Binmahfouz, Rawan H. Hareeri, Rasheed A. Shaik and Amina M. Bagher
Molecules 2023, 28(6), 2741; https://doi.org/10.3390/molecules28062741 - 17 Mar 2023
Cited by 15 | Viewed by 2968
Abstract
Nephrotoxicity is a serious complication that limits the clinical use of gentamicin (GEN). Parthenolide (PTL) is a sesquiterpene lactone derived from feverfew with various therapeutic benefits. However, PTL possesses low oral bioavailability. This study aimed to evaluate the therapeutic protective effects of PTL-phytosomes [...] Read more.
Nephrotoxicity is a serious complication that limits the clinical use of gentamicin (GEN). Parthenolide (PTL) is a sesquiterpene lactone derived from feverfew with various therapeutic benefits. However, PTL possesses low oral bioavailability. This study aimed to evaluate the therapeutic protective effects of PTL-phytosomes against GEN-induced nephrotoxicity in rats. The PTL was prepared as phytosomes to improve the pharmacological properties with a particle size of 407.4 nm, and surface morphology showed oval particles with multiple edges. Rats were divided into six groups: control, nano-formulation plain vehicle, PTL-phytosomes (10 mg/kg), GEN (100 mg/kg), GEN + PTL-phytosomes (5 mg/kg), and GEN + PTL-phytosomes (10 mg/kg). The administration of PTL-phytosomes alleviated GEN-induced impairment in kidney functions and histopathological damage, and decreased kidney injury molecule-1 (KIM-1). The anti-oxidative effect of PTL-phytosomes was demonstrated by the reduced malondialdehyde (MDA) concentration and increased superoxide dismutase (SOD) and catalase (CAT) activities. Furthermore, PTL-phytosomes treatment significantly enhanced sirtuin 1 (Sirt-1), nuclear factor erythroid-2-related factor-2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and heme oxygenase-1 (HO-1). Additionally, PTL-phytosomes treatment exhibited anti-inflammatory and anti-apoptotic properties in the kidney tissue. These findings suggest that PTL-phytosomes attenuate renal dysfunction and structural damage by reducing oxidative stress, inflammation, and apoptosis in the kidney. Full article
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