Search Results (29)

Hepato-renal crosstalk is a complex biological communication between liver and kidneys mediated by various factors, including cellular, endocrine, and paracrine molecules. This interaction highlights the functional consequences that damage in one organ can have on the other. In particular, the liver and kidney play a pivotal role in maintaining body homeostasis, as they are both involved in the excretion of toxic bioproducts and drugs. The overlap of liver and kidney disease has both therapeutic and prognostic implications. Therefore, a better understanding of the mechanisms involved in the pathogenesis of this bidirectional crosstalk is essential for improving the management of these clinical conditions and patient outcomes. Specifically, a multidisciplinary approach involving hepatologists and nephrologists is crucial to reduce the long-term burden of these clinical settings. This review focuses on the hepato-renal crosstalk in the context of liver and kidney disease, with particular attention to acute kidney injury associated with liver injury, hepatorenal syndrome and, chronic kidney disease in the context of liver fibrosis. Full article

Ralstonia eutropha H16, a metabolically versatile bacterium, has gained prominence as a microbial platform for sustainable bioproduction. While its capabilities in synthesizing single-cell proteins and biodegradable materials are well documented, comprehensive strain-level safety evaluations remain insufficient for food-grade applications. This study systematically assessed the safety of R. eutropha H16 through genomic, phenotypic, and toxicological analyzes. Genomic analyzes revealed the absence or minimal presence of virulence factors and antibiotic resistance genes, aligning with microbiological safety standards. Phenotypic investigations demonstrated a limited gastric fluid tolerance (pH 2.5, survival rate 25.70% after 3 h) and intestinal fluid persistence (pH 8, 44.67% viability after 3 h), coupled with an exceptional bile salt tolerance (0.2% w/v). Antioxidant assays confirmed the fermentation broth specifically scavenges DPPH free radicals (14.60 ± 1.24 μg Trolox/mL), whereas bacterial suspensions and cell-free supernatants exhibited a strong hydroxyl radical scavenging (>90 U/mL) and superoxide anion inhibition (>100 U/L). Acute toxicity testing indicated no mortality or histopathological abnormalities, with an LD₅₀ value exceeding 1 × 10¹¹ CFU/kg. Subacute toxicity studies (28-day, 1 × 10⁸–1 × 10¹⁰ CFU/kg) revealed no significant effects on growth, hematology, or organ function. Minor alterations in serum biochemistry might be attributed to physiological adaptation. Subacute exposure induced transient serum ALT fluctuations without hepatorenal dysfunction, while maintaining hematological parameters within physiological ranges. Collectively, these results substantiate the safety of R. eutropha H16 for food-related applications while underscoring the necessity of strain-specific risk assessments for industrial microbial platforms. Full article

The excessive intake of monosodium glutamate (MSG) increases its cellular levels in different organs and induces organ toxicity. The current study aims to investigate the metabolic changes and possible causes of hepatic, renal, and cardiac toxicity induced by MSG overconsumption. Thirty adult male rats were randomly allocated into five groups: control, MSG0.8, MSG1, MSG2, and MSG3, which were orally treated with a daily oral dose of saline, 0.8, 1, 2, and 3 g MSG/kg BW, respectively, for eight weeks. The hepatic, renal, and cardiac biochemical markers; lipid profile; glucose; electrolytes; iNOS; α-KGD; oxidative stress; and inflammatory markers were investigated. The histopathological examination of hepatic and renal tissues was also performed. The results revealed MSG-induced hepato-renal and cardiac toxicity, as indicated by the changes in the biochemical markers and tissue architecture of these organs. The toxicity is observed in the form of dyslipidemia, oxidative stress (increased MDA and NO and decreased GSH, SOD, CAT, and GST), and inflammatory responses (increased TNF-α and IL-6). The histopathological changes in liver and kidney architecture confirmed the obtained results. In conclusion, the MSG-induced hepatic, renal, and cardiac toxicity was dose-dependent, and awareness should be raised about the side effects of the overconsumption of MSG. Full article

Hazardous heavy metals, particularly cadmium (Cd), are widely distributed in the environment and cause oxidative stress in various animal and human organs. Clove oil (CLO), a common aromatic spice, has been used as a traditional medication as it has potent anti-inflammatory, antioxidant, and hepatoprotective properties. Background/Objectives: This study aimed to investigate the antioxidant, antiapoptotic, and anti-inflammatory effects of clove oil (CLO) against hepatorenal toxicity induced by cadmium (Cd). Methods: Twenty rats were equally divided into four groups: a control group, a Cd group treated with 15 mg/kg b.wt CdCl₂, a CLO group administered 200 mg/kg b.wt CLO, and a Cd+CLO group. All groups were orally treated for 4 weeks. Results: Cadmium (Cd) exposure caused anemia and hepatorenal damage, as evidenced by increased serum levels of urea, creatinine, uric acid, total bilirubin (including its direct and indirect fractions), and elevated activities of liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP). However, total protein and albumin levels decreased. Furthermore, there was a decrease in the levels of glutathione, glutathione transferase, and catalase in the liver antioxidant profiles. Meanwhile, malondialdehyde levels increased. Cadmium toxicity caused elevated expression of liver apoptosis markers, such as tumor necrosis factor-alpha (TNF-α) and caspase-3, and inflammation. CLO ameliorated the oxidative effects of Cd through decreasing urea (27.4%), creatinine (41.6%), liver enzymes, and hepatic apoptotic markers while increasing levels of total protein, albumin, and hepatic values of SOD (60.37%), CAT (64.49%), GSH (50.41%), and GST (9.16%). Conclusions: Hematological and biochemical parameters, as well as the antioxidant system, improved following clove oil treatment, leading to a reduction in hepatorenal damage. Therefore, it is possible to conclude that CLO protects rats from inflammation, apoptosis, and hepatorenal oxidative damage caused by Cd poisoning. Comprehensive translational research is required to validate CLO’s efficacy and safety of use in humans. Future studies should focus on elucidating the precise molecular mechanisms, optimal dosing strategies, and potential synergistic effects of CLO with other therapeutic agents. Full article

Background: Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. Objectives: We conducted a systematic review and meta-analysis to determine chemotoxicity’s prevalence and risk factors in CRC. Methods: A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. Results: Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: −1.44) and GI toxicity (β:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). Conclusions. Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy. Full article

Exposure to mercuric chloride (HgCl₂), either accidental or occupational, induces substantial liver and kidney damage. Coenzyme Q10 (CoQ10) is a natural antioxidant that also has anti-inflammatory and anti-apoptotic activities. Herein, our study aimed to investigate the possible protective effects of CoQ10 alone or loaded with albumin nanoparticles (CoQ10NPs) against HgCl₂-induced hepatorenal toxicity in rats. Experimental animals received CoQ10 (10 mg/kg/oral) or CoQ10NPs (10 mg/kg/oral) and were injected intraperitoneally with HgCl₂ (5 mg/kg; three times/week) for two weeks. The results indicated that CoQ10NP pretreatment caused a significant decrease in serum liver and kidney function markers. Moreover, lowered MDA and NO levels were associated with an increase in antioxidant enzyme activities (SOD, GPx, GR, and CAT), along with higher GSH contents, in both the liver and kidneys of intoxicated rats treated with CoQ10NPs. Moreover, HgCl₂-intoxicated rats that received CoQ10NPs revealed a significant reduction in the hepatorenal levels of TNF-α, IL-1β, NF-κB, and TGF-β, as well as an increase in the hepatic level of the fibrotic marker (α-SMA). Notably, CoQ10NPs counteracted hepatorenal apoptosis by diminishing the levels of Bax and caspase-3 and boosting the level of Bcl-2. The hepatic and renal histopathological findings supported the abovementioned changes. In conclusion, these data suggest that CoQ10, alone or loaded with albumin nanoparticles, has great power in reversing the hepatic and renal tissue impairment induced by HgCl₂ via the modulation of hepatorenal oxidative damage, inflammation, and apoptosis. Therefore, this study provides a valuable therapeutic agent (CoQ10NPs) for preventing and treating several HgCl₂-induced hepatorenal disorders. Full article

Background and Objectives: Paracetamol overdose is a significant global issue due to its widespread use, which can lead to a lack of awareness regarding its potential side effects. Paracetamol can harm the liver, possibly resulting in liver failure. Conversely, this study employed extracts from Petroselinum crispum (PC), known for its rich content of bioactive compounds, with demonstrated antioxidant properties shown in previous research as well as protective effects against various diseases. The primary objective of this study was to investigate the potential protective effects of Petroselinum crispum on altered hematological and biochemical parameters in the blood of rats exposed to paracetamol. Materials and Methods: The study involved twenty Wistar rats divided into four groups. Different groups of male rats were administered PC extract at 200 mg/kg body weight daily for 15 days, along with a standard reference dose of paracetamol at 200 mg/kg. The study assessed hepatoprotection capacity by analyzing liver enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin, albumin, and lipid profiles. Renal safety was evaluated through creatinine, urea, uric acid, lactate dehydrogenase (LDH), and total protein. Additionally, histopathological examinations of the liver and kidneys were conducted. Results: Following Paracetamol overdose, there were reductions in hemoglobin levels, serum total protein, albumin, and uric acid. Paracetamol overdose also elevated levels of several blood biomarkers, including creatinine, urea, nitrogen, ALT, AST, triglycerides, LDH activity, white blood cell count, and platelet count compared to the control group. However, using an ethanolic extract of Petroselinum crispum significantly mitigated the severity of these alterations and the extent of the effect correlated with the dose administered. Parsley extract helped prevent proteinuria and low hemoglobin, which are common side effects of Paracetamol. Conclusions: Therefore, parsley may hold promise in managing liver and kidney conditions—particularly in addressing proteinuria. Ultimately, these results may have implications for human health by potentially mitigating paracetamol-induced renal, hepatic, and hematological toxicity. Full article

Tetrodotoxin (TTX) is a highly toxic compound detected in various edible marine animals even in European waters. To characterize the hazard by oral exposure to TTX, its tissue distribution was evaluated after single (75 μg/kg) or 7-day (25–125 μg/kg) oral administration in mice. Moreover, TTX liver and renal toxicity was evaluated after 7-day oral administration. The elimination cycle of a single oral dose of TTX (75 µg/kg) was found to be approximately 168 h (7 days). Daily oral administration of TTX at doses of 25, 75, and 125 µg/kg for 7 consecutive days revealed dose-dependent toxic effects on the liver and kidney. Histopathological examination showed increased inflammatory cell infiltration in the liver and kidney with higher TTX doses, along with disorganization of the hepatic cord and renal tubular cell arrangement. The study results indicated that TTX had more hepatotoxicity than nephrotoxicity in mice. These findings provide insights into the unintentional ingestion of a low dose of TTX in mammals, including humans, and emphasize the importance of food safety. Full article

Cisplatin is a widely used antineoplastic drug, though its adverse effects, particularly its hepatorenal toxicity, limit its long-term application. Sika deer antler is a valuable traditional Chinese medicine (TCM) documented to possess the capacity for tonifying the kidney and regulating the liver, of which the sika deer antler protein is an important active ingredient. In this study, two protein fractions, SVPr1 and SVPr2, of sika deer antler were purified and administered to mice treated with cisplatin, and serum metabolome and fecal microbiota were measured using ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) and 16S rRNA gene sequencing. SVPr1 and SVPr2 significantly ameliorated cisplatin-induced liver and kidney injury and reduced mitochondrial dysfunction, oxidative stress, inflammatory response, and apoptosis. In addition, SVPr1 and SVPr2 impacted the gut microbiota structure of mice, significantly increasing the relative abundances of Lactobacillus, which deserves to be scrutinized. Moreover, SVPr1 and SVPr2 antagonism of cisplatin-induced hepatorenal injury may be related to the regulation of lysine degradation, tryptophan metabolism, and riboflavin metabolism pathways, significantly altering the levels of L-saccharopine, L-lysine, L-kynurenine, 3-methylindole, xanthurenic acid, riboflavin, and D-ribulose-5-phosphate. A correlation between the differential metabolites and Lactobacillus was identified. These findings increased the knowledge of the gut microbiota–metabolites axis mediated by SVPr1 and SVPr2, and may be able to contribute to the development of new therapeutic strategies for the simultaneous prevention and treatment of liver and kidney injury from cisplatin treatment. Full article

Phthalates are widely distributed in our environment due to their usage in many industries, especially in plastic production, which has become an essential part of daily life. This investigation aimed to assess the potential remedial influence of lutein, a naturally occurring carotenoid, on phthalate-triggered damage to the liver and kidneys. When di-(2-ethylhexyl) phthalate (DEHP) was administered to male albino rats over sixty straight days at a dosage of 200 mg/kg body weight, it resulted in a significant increase in the serum activity of liver enzymes (AST, ALT, and GGT), alpha-fetoprotein, creatinine, and cystatin-C, as well as disruptions in the serum protein profile. In addition, intoxication with DEHP affected hepato-renal tissues’ redox balance. It increased the content of some proinflammatory cytokines, nuclear factor kappa B (Nf-κB), and apoptotic marker (caspase-3); likewise, DEHP-induced toxicity and decreased the level of anti-apoptotic protein (Bcl-2) in these tissues. Lutein administration at a dose level of 40 mg/kg b.w efficiently facilitated the changes in serum biochemical constituents, hepato-renal oxidative disturbance, and inflammatory, apoptotic, and histopathological alterations induced by DEHP intoxication. In conclusion, it can be presumed that lutein is protective as a natural carotenoid against DEHP toxicity. Full article

In our life scenarios, we are involuntarily exposed to many heavy metals that are well-distributed in water, food, and air and have adverse health effects on animals and humans. Cadmium (Cd) is one of the most toxic 10 chemicals reported by The World Health Organization (WHO), affecting organ structure and function. In our present study, we use one of the green microalga Chlorella vulgaris (ChV, 500 mg/kg body weight) to investigate the beneficial effects against CdCl₂-induced hepato-renal toxicity (Cd, 2 mg/kg body weight for 10 days) on adult male Sprague-Dawley rats. In brief, 40 adult male rats were divided into four groups (n = 10); Control, ChV, Cd, and Cd + ChV. Cadmium alters liver and kidney architecture and disturbs the cellular signaling cascade, resulting in loss of body weight, alteration of the hematological picture, and increased ALT, AST, ALP, and urea in the blood serum. Moreover, cadmium puts hepatic and renal cells under oxidative stress due to the up-regulation of lipid peroxidation resulting in a significant increase in the IgG level as an innate immunity protection and induction of the pro-inflammatory cytokines (IL-1β and TNF-α) that causes hepatic hemorrhage, irregular hepatocytes in the liver and focal glomeruli swelling and proximal tubular degeneration in the kidney. ChV additive to CdCl₂, could organize the protein translation process via NF-kB/Nrf2 pathways to prevent oxidative damage by maintaining cellular redox homeostasis and improving the survival of and tolerance of cells against oxidative damage caused by cadmium. The present study shed light on the anti-inflammatory and antioxidative properties of Chlorella vulgaris that suppress the toxicity influence of CdCl₂. Full article

Heavy metal toxicity is an important issue owing to its harmful influence on fish. Hence, this study is a pioneer attempt to verify the in vitro and in vivo efficacy of a magnetite (Fe₃O₄) nanogel (MNG) in mitigating waterborne lead (Pb) toxicity in African catfish. Fish (n = 160) were assigned into four groups for 45 days. The first (control) and second (MNG) groups were exposed to 0 and 1.2 mg L⁻¹ of MNG in water. The third (Pb) and fourth (MNG + Pb) groups were exposed to 0 and 1.2 mg L⁻¹ of MNG in water and 69.30 mg L⁻¹ of Pb. In vitro, the MNG caused a dramatic drop in the Pb level within 120 h. The Pb-exposed group showed the lowest survival (57.5%) among the groups, with substantial elevations in hepato-renal function and lipid peroxide (MDA). Moreover, Pb exposure caused a remarkable decline in the protein-immune parameters and hepatic antioxidants, along with higher Pb residual deposition in muscles and obvious histopathological changes in the liver and kidney. Interestingly, adding aqueous MNG to Pb-exposed fish relieved these alterations and increased survivability. Thus, MNG is a novel antitoxic agent against Pb toxicity to maintain the health of C. gariepinus. Full article

Aflatoxin B1 (AFB₁) is a recalcitrant metabolite produced by fungi species, and due to its intoxications in animals and humans, it has been classified as a Group 1 carcinogen in humans. Preserving food products with Sorghum bicolor sheath can minimise the contamination of agricultural products and avert ill health occasioned by exposure to AFB₁. The current study investigated the ameliorating effect of Sorghum bicolor sheath hydrophobic extract (SBE-HP) enriched in Apigenin (API) on the hepatorenal tissues of rats exposed to AFB1. The SBE-HP was characterised using TLC and LC-MS and was found to be enriched in Apigenin and its methylated analogues. The study used adult male rats divided into four experimental cohorts co-treated with AFB1 (50 µg/kg) and SBE-HP (5 and 10 mg/kg) for 28 days. Biochemical, enzyme-linked immunosorbent assays (ELISA) and histological staining were used to examine biomarkers of hepatorenal function, oxidative status, inflammation and apoptosis, and hepatorenal tissue histo-architectural alterations. Data were analysed using GraphPad Prism 8.3.0, an independent t-test, and a one-way analysis of variance. Co-treatment with SBE-HP ameliorated an upsurge in the biomarkers of hepatorenal functionality in the sera of rats, reduced the alterations in redox balance, resolved inflammation, inhibited apoptosis, and preserved the histological features of the liver and kidney of rats exposed to AFB₁. SBE-HP-containing API is an excellent antioxidant regiment. It can amply prevent the induction of oxidative stress, inflammation, and apoptosis in the hepatorenal system of rats. Therefore, supplementing animal feeds and human foods with SBE-HP enriched in Apigenin may reduce the burden of AFB1 intoxication in developing countries with a shortage of effective antifungal agents. Full article

Irinotecan (CPT-11) is a chemotherapeutic agent involved in the treatment regimens for several malignancies such as colorectal cancer. N-acetylcysteine (NAC) is a strong antioxidant and anti-inflammatory agent used in the treatment of several diseases related to oxidative stress and inflammation. This study aimed at investigating whether NAC provides protection against hepatorenal and gastrointestinal tissue damage induced by CPT-11. Thirty-two Wistar albino rats were divided into four groups as control, NAC, CPT-11, and CPT-11+NAC. Following the experimental period, blood, and tissue samples (liver, kidney, stomach, and small intestine) were collected, and biochemical indicators, together with pro-inflammatory cytokines (TNF-α and IL-1β), matrix metalloproteinases (MMPs), malondialdehyde (MDA), glutathione peroxidase (GPx) and superoxide dismutase (SOD) levels were evaluated. Both the biochemical indicators and the pro-inflammatory cytokines, MMP, and MDA levels increased in animals treated with CPT-11, while SOD and GPx activities decreased. Histopathological evaluation revealed structural damage in all examined tissues. With NAC administration, significant improvements were observed, both biochemically and histologically. In conclusion, the results of the present study suggest that NAC treatment together with CPT-11 may have a beneficial effect on reducing CPT-11 toxicity in rats, by modulating inflammation and the oxidant–antioxidant balance. These results strongly promote further investigative studies. Full article

Cyperus species represent a group of cosmopolitan plants used in folk medicine to treat several diseases. In the current study, the phytochemical profile of Cyperus laevigatus ethanolic extract (CLEE) was assessed using UPLC-QTOF–MS/MS. The protective effect of CLEE at 50 and 100 mg /kg body weight (b.w.) was evaluated on hepatorenal injuries induced by thioacetamide (100 mg/kg) via investigation of the extract’s effects on oxidative stress, inflammatory markers and histopathological changes in the liver and kidney. UPLC-QTOF–MS/MS analysis of CLEE resulted in the identification of 94 compounds, including organic and phenolic acids, flavones, aurones, and fatty acids. CLEE improved the antioxidant status in the liver and kidney, as manifested by enhancement of reduced glutathione (GSH) and coenzyme Q10 (CoQ10), in addition to the reduction in malondialdehyde (MDA), nitric oxide (NO), and 8-hydroxy-2′-deoxyguanosine (8OHdG). Moreover, CLEE positively affected oxidative stress parameters in plasma and thwarted the depletion of hepatorenal ATP content by thioacetamide (TAA). Furthermore, treatment of rats with CLEE alleviated the significant increase in plasma liver enzymes, kidney function parameters, and inflammatory markers. The protective effect of CLEE was confirmed by a histopathological study of the liver and kidney. Our results proposed that CLEE may reduce TAA-hepatorenal toxicity via its antioxidant and anti-inflammatory properties suppressing oxidative stress. Full article