Search Results (23)

Background/Objectives: Perioperative risk stratification in cardiac surgery is based mainly on static preoperative variables and therefore does not fully capture dynamic multiorgan responses to surgical stress. The Model for End-Stage Liver Disease (MELD) score, which integrates bilirubin, creatinine, and the international normalized ratio (INR), reflects hepatorenal function, but its perioperative dynamics remain insufficiently explored. This study aimed to characterize perioperative MELD trajectories in patients undergoing off-pump coronary artery bypass grafting (OPCAB) and to assess the influence of sex and diabetes mellitus on these changes and their clinical relevance. Methods: This retrospective observational study included 111 patients undergoing elective OPCAB. MELD scores were assessed preoperatively (MELD₀), on postoperative day 1 (MELD₁), and on day 6 (MELD₆). Dynamic indices of MELD change were calculated, including the early postoperative increase (ΔMELD₀₁). The effects of sex and diabetes mellitus on MELD trajectories were analyzed using multivariable linear regression and generalized estimating equations. A high-surge phenotype was defined as the upper quartile of ΔMELD₀₁. Results: MELD increased significantly on postoperative day 1 and partially recovered by day 6 (p < 0.001). Female sex was independently associated with lower postoperative MELD values (β = −2.54, p < 0.001) and a smaller ΔMELD₀₁, whereas diabetes mellitus was associated with a reduced MELD rise (β = −1.07, p = 0.028). Patients with a high-surge MELD phenotype had significantly longer hospitalization than those with a lower MELD response (12.8 ± 2.1 vs. 9.2 ± 1.2 days, p < 0.001). Conclusions: Perioperative MELD trajectories reflect a dynamic hepatorenal stress response after OPCAB and may improve identification of clinically relevant physiological vulnerability. Full article

Objective: The aim of this study was to develop and evaluate non-antibiotic strategies against Helicobacter pylori by establishing a bovine immune milk platform and designing a synergistic multi-antigen immunogen to enhance humoral immune responses. Methods: Inactivated Helicobacter pylori (H. pylori) was used to immunize dairy cows, and the resulting immune milk was characterized for antibody specificity, acid stability, and target antigens via ELISA, Western blot, agglutination assays, and mass spectrometry. Key identified antigens (UreA, UreB, UreE, UreG, HypA, FlaA, and FlaB) were produced as recombinant proteins. Their immunogenicity was evaluated in a murine model, comparing single antigens with various protein combinations. Immune responses were assessed by antigen-specific IgG ELISA, bacterial agglutination titers, flow cytometry for T-cell activation, and histopathology for safety. Results: Immune milk contained high-titer, acid-stable IgG antibodies targeting multiple H. pylori virulence factors. In mice, while single proteins induced specific IgG, a multi-antigen cocktail (FlaA + FlaB + HypA + UreA + UreB + UreE + UreG) elicited significantly higher serum agglutination titers (~7 × 10³) than single antigens or inactivated whole-cell vaccine, alongside robust CD4⁺ T-cell activation. No formulations showed any hepatorenal or splenic toxicity. Conclusion: Bovine immune milk is a viable platform for acid-stable antibody delivery. A rationally designed multi-antigen cocktail synergistically enhances functional humoral immunity in vivo, providing a promising foundation for developing antibody-based or subunit vaccine strategies against H. pylori. Full article

Chronic exposure to pesticides poses significant hepatorenal toxicity risks, yet a systematic comparison of their effects across species and tissues is lacking. In this study, we systematically evaluated the cytotoxicity of eight pesticides using human (CCC-HEL-1 hepatocytes; 293T renal cells) and rodent (IAR hepatocytes; NRK renal cells) cellular models. Our results showed substantial variations in potency, with chlorothalonil exhibiting the highest toxicity (IC50 = 32.55 mg/L in 293T cells) and chlorpyrifos the lowest (IC50 = 444.5 mg/L in 293T cells). Principal component analysis revealed distinct species- and tissue-specific response patterns, highlighting the unique resistance of NRK cells. Mechanistic investigations demonstrated organ-specific biomarker alterations, such as elevated hepatic ALP and suppressed renal KIM-1. Remarkably, the MRP2 transporter exhibited tissue-specific divergence, being significantly downregulated in renal cells (all 8 pesticides, p < 0.005) and most hepatic cells (7/8 pesticides, p < 0.05), while propiconazole uniquely upregulated it in hepatocytes (1.5-fold, p < 0.05). Collectively, these findings offer critical mechanistic insights into pesticide-specific toxicity and cross-species susceptibility, providing valuable data to improve human health risk assessment in food safety and toxicology. Full article

Copper is an essential trace element that supports numerous physiological functions; however, excessive copper accumulation can disrupt cellular and biological processes. In this study, forty-eight male mice were randomly divided into four groups (n = 12): Control (fed normal rice), Cu300 (300 mg/kg copper), Cu300+Se (Cu300 + selenium-enriched rice), and Cu300+iSe (Cu300 + 1 mg/kg iSe), and were treated for 180 days. Copper exposure resulted in reduced body weight, hepatomegaly and nephritis, elevated copper deposition in organs, oxidative stress, and significant declines in RBC, HGB, and WBC counts, leading to anemia and immunosuppression. Selenium supplementation, effectively mitigated these effects by reducing copper accumulation, restoring antioxidant balance, and enhancing selenoprotein-related functions. Histopathological analysis revealed that copper toxicity induced hydropic degeneration and focal necrosis in hepatic and renal tissues, effects that were significantly attenuated by selenium supplementation. Transcriptomic profiling revealed that selenium-enriched rice reversed copper-induced gene expression changes. In the liver, selenium treatment significantly upregulated protective genes such as Slc7a, Bola1, Uqcrq, Dtx1, and Znrd2, while downregulating stress-related genes like Trim75, Dpm3, Moxd1, Tnfrsf25, and Gpr75. In the kidneys, selenium enhanced the expression of detoxification and immune-modulating genes (Mt1, Mt2, Rhbdl1, Crisp3, Mif) and suppressed stress-related genes (Nnt, Ifi44l, NLRP12, Eno1b, Ugt1a), demonstrating its role in mitigating oxidative and inflammatory stress. Collectively, these findings demonstrate that selenium-enriched rice exerts potent protective effects against chronic copper toxicity through multiple mechanisms: (1) restoration of mitochondrial function, (2) attenuation of ER stress and apoptosis, (3) enhancement of antioxidant and detoxification pathways, and (4) modulation of metabolic and immune responses. This study highlights selenium-enriched rice as a promising nutritional intervention for mitigating chronic copper toxicity and maintaining hepatorenal health. Full article

Sepsis, defined as a dysregulated host response to infection, is one of the leading causes of mortality worldwide. It unleashes in the organism a cascade of molecules, cytokines, and proteins which leads to an inflammatory storm. If this response to infection is uncontrolled, any organ is susceptible to damage. Acute kidney injury (AKI) is one of the most frequent organ dysfunctions in septic patients, and while it can be reversible, its presence leads to a higher burden of morbidity and mortality. While serum creatinine is essential in evaluating kidney function, the pathophysiology of AKI is not completely elucidated, and a plethora of novel biomarkers have been studied in the hope of an early diagnosis and fast treatment. While the liver is not as affected by sepsis, it plays an important role as a guardian by providing acute-phase proteins, activating neutrophils, and controlling iron balance. Acute liver failure (ALF) could impair the organism’s capacity to contain and eliminate pathogens. Some molecules have been associated with either AKI or ALF, although biomarkers specific for organ dysfunction are difficult to validate. The aim of this review is to understand the role of several molecules in the pathophysiology of sepsis and their clinical ability for diagnosing or predicting sepsis-induced hepato-renal dysfunction. 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

Background/Objectives: Alcohol can directly damage the liver, causing steatosis, steatohepatitis, cirrhosis, and hepatocellular cancer. The aim of this study was to examine 28-day survival in hospitalized patients with alcohol-related liver disease (ALD) cirrhosis, as well as to develop and validate a new survival prediction model. Methods: A total of 145 patients with ALD cirrhosis were included; 107 were diagnosed with acute decompensation (AD) and 38 with acute-on-chronic liver failure (ACLF). The new liver mortality inpatients (LIV-IN) score was calculated using the following variables: hepatic encephalopathy (HE), hepatorenal syndrome (HRS), ascites, systemic inflammatory response syndrome (SIRS), community-acquired infection (CAI), and fibrinogen. The diagnostic accuracy of the LIV-IN score was tested, along with the model for end-stage liver disease (MELD), model for end-stage liver disease-sodium (MELD-Na), albumin-bilirubin (ALBI), neutrophil-to-lymphocyte ratio (NLR), chronic liver failure consortium-C acute decompensation (CLIF-C AD), and chronic liver failure consortium-acute-on-chronic liver failure (CLIF-C ACLF). Results: Lethal outcome occurred in 46 (31.7%) patients. The mortality rate was higher in the ACLF group (n = 22, 57.9%) compared to the AD group (n = 24, 22.4%) (p < 0.01). The highest predictive power for short-term mortality was observed for the LIV-IN score (AUC 73.4%, p < 0.01). In patients with AD, the diagnostic accuracy of the CLIF-C AD score was better than for the LIV-IN score (AUC 0.699; p = 0.004, AUC 0.686; p = 0.007, respectively). In patients with ACLF, only the LIV-IN score had statistically significant discriminative power in predicting 28-day survival. Conclusions: The liver mortality inpatients prognostic score is a new, reliable prognostic model in predicting 28-day mortality. Full article

Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment. Full article

In patients with portal hypertension, there are many complications including cardiovascular abnormalities, hepatorenal syndrome, ascites, variceal bleeding, and hepatic encephalopathy. The underlying mechanisms are not yet completely clarified. It is well known that portal hypertension causes mesenteric congestion which produces reactive oxygen species (ROS). ROS has been associated with intestinal mucosal injury, increased intestinal permeability, enhanced gut bacterial overgrowth, and translocation; all these changes result in increased endotoxin and inflammation. Portal hypertension also results in the development of collateral circulation and reduces liver mass resulting in an overall increase in endotoxin/bacteria bypassing detoxication and immune clearance in the liver. Endotoxemia can in turn aggravate oxidative stress and inflammation, leading to a cycle of gut barrier dysfunction → endotoxemia → organ injury. The phenotype of cardiovascular abnormalities includes hyperdynamic circulation and cirrhotic cardiomyopathy. Oxidative stress is often accompanied by inflammation; thus, blocking oxidative stress can minimize the systemic inflammatory response and alleviate the severity of cardiovascular diseases. The present review aims to elucidate the role of oxidative stress in cirrhosis-associated cardiovascular abnormalities and discusses possible therapeutic effects of antioxidants on cardiovascular complications of cirrhosis including hyperdynamic circulation, cirrhotic cardiomyopathy, and hepatorenal syndrome. Full article

Type 2 diabetes (T2D) is a chronic metabolic condition associated with obesity, oxidative stress-mediated inflammation, apoptosis, and impaired insulin signaling. The utilization of phytochemical therapy generated from plants has emerged as a promising approach for the treatment of diabetes and its complications. Kiwifruit is recognized for its substantial content of antioxidative phenolics. Therefore, this work aimed to examine the effect of Actinidia deliciosa (kiwi fruit) on hepatorenal damage in a high-fat diet (HFD) and streptozotocin (STZ)-induced T2D in rats using in vivo and in silico analyses. An increase in hepatic and renal lipid peroxidation was observed in diabetic rats accompanied by a decrease in antioxidant status. Furthermore, it is important to highlight that there were observable inflammatory and apoptotic responses in the hepatic and renal organs of rats with diabetes, along with a dysregulation of the phosphorylation levels of mammalian target of rapamycin (mTOR), protein kinase B (Akt), and phosphoinositide 3-kinase (PI3K) signaling proteins. However, the administration of kiwi extract to diabetic rats alleviated hepatorenal dysfunction, inflammatory processes, oxidative injury, and apoptotic events with activation of the insulin signaling pathway. Furthermore, molecular docking and dynamic simulation studies revealed quercetin, chlorogenic acid, and melezitose as components of kiwi extract that docked well with potential as effective natural products for activating the silent information regulator 1(SIRT-1) pathway. Furthermore, phenolic acids in kiwi extract, especially syringic acid, P-coumaric acid, caffeic acid, and ferulic acid, have the ability to inhibit the phosphatase and tensin homolog (PTEN) active site. In conclusion, it can be argued that kiwi extract may present a potentially beneficial adjunctive therapy approach for the treatment of diabetic hepatorenal complications. 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

Background and objectives: Oleanolic acid (OA) is a penta-cyclic triterpene with diverse bioactivities such as anticarcinogenic, antiviral, antimicrobial, hepatoprotective, anti-atherosclerotic, hypolipidemic, and gastroprotective. However, its effects on hepatorenal damage remain unclear. The protective activity of OA, separated from Viscum schimperi (Loranthaceae), against TAA (thioacetamide)-produced acute hepatic and renal damage was explored. Materials and Methods: Mice were treated with OA for 7 days before TAA (200 mg/kg, i.p.). Serum indices of hepatorenal injury, pathological lesions, molecular biological indexes, and inflammatory/apoptotic genes were estimated. Results: The tissues of both organs were greatly affected by the TAA injection. That was evident through increased serum markers of hepato-renal injury as well as remarkable histopathological lesions. TAA-induced injury was associated with oxidative and inflammatory responses in both organs as there was an elevation of oxidative stress parameters (4-HNE (4-hydroxy-nonenal), MDA (malondialdehyde), NOx (nitric oxide)), decline of antioxidants (reduced glutathione (GSH), superoxide dismutase (SOD), and total antioxidant capacity (TAC)), and an increase in the gene expression/level of inflammatory mediators (interleukins (1β&6)). The inflammatory response was linked to a significant activation of NF-κB (nuclear-factor kappa-B)/TNF-α (tumor-necrosis factor-alpha) signaling. The inflammatory response in both organs was accompanied by apoptotic changes, including a rise in the gene expression and level of apoptotic parameters (caspase-3 and Bax) along with a decline in Bcl-2 (anti-apoptotic parameter) gene expression and level. These pathogenic events were found to be closely related to the suppression of the antioxidant signaling pathway, Nrf2 (nuclear-factor erythroid 2–related factor-2)/SIRT1 (sirtuin-1)/HO-1 (heme-oxygenase 1). On the other hand, OA significantly ameliorated TAA-induced injury in both organs. On the other hand, OA counterpoised the inflammatory response as it ameliorated NF-κB/TNF-α signaling and cytokine release. OA enhanced Nrf2/SIRT1/HO-1 signaling and counteracted apoptotic damage. Conclusions: OA showed anti-inflammation and antiapoptotic capacities that effectively suppressed TAA-induced acute hepatorenal damage. Full article

Cepabiflas B and C (CBs) are flavonoid dimers separated from Allium cepa. They demonstrated antioxidant and α-glucosidase and protein tyrosine phosphatase 1B inhibition capacities. However, their anti-inflammatory activities and their effects on endotoxemia are unknown. The current study aimed at exploring the protective activities of CBs on lipopolysaccharide (LPS)-induced kidney and liver damage in mice and investigating the possible molecular mechanisms. Mice were orally treated with a low (40 mg/kg) or high (60 mg/kg) dose of CBs for five days prior to a single intraperitoneal injection of LPS (10 mg/kg). Samples of serum and hepatic and kidney tissues were collected 24 h after the LPS challenge. Changes in serum indices of hepatic and renal injury, pathological changes, molecular biological parameters, and proteins/genes related to inflammation and apoptosis of these organs were estimated. LPS injection resulted in deleterious injury to both organs as indicated by elevation of serum ALT, AST, creatinine, and BUN. The deteriorated histopathology of hepatic and renal tissues confirmed the biochemical indices. CBs treated groups showed a reduction in these parameters and improved histopathological injurious effects of LPS. LPS-induced hepatorenal injury was linked to elevated oxidative stress as indicated by high levels of MDA, 4-HNE, as well as repressed antioxidants (TAC, SOD, and GSH) in hepatic and kidney tissues. This was accompanied with suppressed Nrf2/HO-1 activity. Additionally, there was a remarkable inflammatory response in both organs as NF-κB signalling was activated and high levels of downstream cytokines were produced following the LPS challenge. Apoptotic changes were observed as the level and gene expression of Bax and caspase-3 were elevated along with declined level and gene expression of Bcl2. Interestingly, CBs reversed all these molecular and genetic changes and restricted oxidative inflammatory and apoptotic parameters after LPS-injection. Collectedly, our findings suggested the marked anti-inflammatory and anti-apoptotic activity of CBs which encouraged its use as a new candidate for septic patients. Full article

The present study evaluated the impact of chronic herbicide (oxyfluorfen; OXY) exposure on catfish, Clarias gariepinus, in terms of growth, hematobiochemical parameters, immune response, antioxidant- and immune-related gene expression, and resistance to monogenean parasites, Quadriacanthus aegypticus. In addition, the protective role of Wormwood, Artemisia cina (AC) against OXY exposure through diet inclusion was also analyzed. The catfish fingerlings were exposed to OXY (1.16 mg/L) for 60 days and fed diets without AC supplementation (control) and with 5% AC supplementation. The results demonstrated that exposure to OXY stunted growth; decreased survival, erythrograms and leukograms, serum protein, and acetylcholinesterase; and negatively altered the antioxidant status. On the contrary, AC supplementation significantly reduced OXY’s negative impacts on growth and hematological, biochemical, and antioxidant balance. In addition, exposure to OXY markedly increased levels of biomarkers of hepatorenal damage, stress indicators, and DNA damage, which were alleviated with AC supplementation. OXY exposure induced immunosuppression manifested by a decrease in lysozyme activities, complement c3, nitric oxide levels, and phagocytic activity. Furthermore, exposure to OXY negatively regulated the expression of immune-antioxidant genes (CAT, GPX1, SOD1, GST, and TGF-Β1). However, it upregulated the expression of CYP1a, IL-1β, and TNF-α in the liver, anterior kidney, and intestine of C. gariepinus. Meanwhile, the addition of AC to the OXY-exposed fish diets notably restored immune components and remedied the altered immune-related gene expressions. Likewise, the AC supplementation significantly alleviated the OXY-induced reduction in the fish survival rate after Q. aegypticus challenge. Accordingly, AC dietary supplementation in catfish diets could alleviate the negative impact of exposure to OXY on growth performance, physiological status, and some immune-antioxidant-related gene expression. Full article

A new insight into the synthesis of the herbal plant (White poplar, Poplus alba) leave extract using chitosan nanocapsule was studied. The in vitro antibacterial activity of chitosan white poplar nanocapsule (CWPNC) against Streptococcus agalactiae (S. agalactiae) was determined. About 120 fish were categorized for 7 days into four groups. The first and second (CWPNC) groups were treated with 0 mg/L and 3 mg/L CWPNC in the water, respectively, without being challenged; the first group was a control. The third (S. agalactiae) and fourth (CWPNC + S. agalactiae) groups were treated with 0 and 3 mg/L CWPNC, respectively, and challenged with S. agalactiae (0.5 × 10⁷ CFU/mL). The obtained results revealed that CWPNC had an in vitro antibacterial activity against S. agalactiae. Moreover, S. agalactiae infection caused a significant elevation (p < 0.05) in the lipid peroxidation (malondialdehyde) and hepatorenal biomarkers, as well as the lowest significant (p < 0.05) survival rate (33.33%). Moreover, a significant depletion (p < 0.05) in the level of antioxidants (catalase and superoxide dismutase) and the immune indicators (immunoglobulin, lysozyme activity, and complement 3) were the consequences of S. agalactiae infection. Treatment of the infected fish with 3 mg/L CWPNC alleviated these bad circumstances. Full article