Hepatorenal Injury Research Articles

Resveratrol mitigates diclofenac-induced hepatorenal toxicity in rats via modulation of miR-144/Nrf2/GSH axis.

Despite the extensive therapeutic uses of diclofenac, it may cause several adverse effects, including hepatorenal injury. The antioxidant and anti-inflammatory properties of resveratrol, a polyphenolic compound, make the agent effective in ameliorating a variety of drug-induced injuries. This study investigated the potential beneficial effects of resveratrol on diclofenac-induced hepatorenal toxicity and explored the role of miR-144 and its relationship to oxidative stress and inflammation triggered by diclofenac. Rats were divided into four groups: control; diclofenac group received diclofenac (10 mg/kg/day, intraperitoneal [ip]) for 7 days; prevention group received resveratrol concomitantly with diclofenac for 7 days; and the treatment group received diclofenac for 7 days followed by resveratrol (20 mg/kg/day, per oral) for another 7 days. Diclofenac administration induced a significant increase in serum hepatorenal biomarkers and histopathological aberrations. In addition, diclofenac upregulated miR-144 while reducing nuclear factor erythroid 2-related factor 2 (Nrf2) protein levels and glutathione (GSH) content. Moreover, diclofenac induced tissue inflammation and apoptosis as evidenced by increased protein expression of nuclear factor kappa B (NF-κB), tumor necrosis factor α (TNF-α), and caspase-3. Intriguingly, resveratrol prevention or treatment significantly mitigated the toxic effects of diclofenac as manifested by normalization of the hepatorenal functions and amelioration of the histopathological changes. Resveratrol also triggered miR-144 downregulation with Nrf2 upregulation. Consequently, resveratrol showed hepatorenal antioxidant, anti-inflammatory, and antiapoptotic activities as manifested by improvement in the antioxidant markers along with a decline in NF-κB, TNF-α, and caspase-3 expressions. In conclusion, this study demonstrates a potential therapeutic role of resveratrol in mitigating diclofenac-induced hepatorenal insult, possibly via modulating miR-144/Nrf2/GSH axis.

Ginseng® Alleviates Malathion-Induced Hepatorenal Injury through Modulation of the Biochemical, Antioxidant, Anti-Apoptotic, and Anti-Inflammatory Markers in Male Rats

This study aims to see if Ginseng® can reduce the hepatorenal damage caused by malathion. Four groups of forty male Wistar albino rats were alienated. Group 1 was a control group that got orally supplied corn oil (vehicle). Group 2 was intoxicated by malathion dissolved in corn oil orally at 135 mg/kg/day. Group 3 orally received both malathion + Panax Ginseng® (300 mg/kg/day). Group 4 was orally given Panax Ginseng® at a 300 mg/kg/day dose. Treatments were administered daily and continued for up to 30 consecutive days. Malathion’s toxic effect on both hepatic and renal tissues was revealed by a considerable loss in body weight and biochemically by a marked increase in liver enzymes, LDH, ACP, cholesterol, and functional renal markers with a marked decrease in serum TP, albumin, and TG levels with decreased AchE and Paraoxonase activity. Additionally, malondialdehydes, nitric oxide (nitrite), 8-hydroxy-2-deoxyguanosine, and TNFα with a significant drop in the antioxidant activities were reported in the malathion group. Malathion upregulated the inflammatory cytokines and apoptotic genes, while Nrf2, Bcl2, and HO-1 were downregulated. Ginseng® and malathion co-treatment reduced malathion’s harmful effects by restoring metabolic indicators, enhancing antioxidant pursuit, lowering the inflammatory reaction, and alleviating pathological alterations. So, Ginseng® may have protective effects against hepatic and renal malathion-induced toxicity on biochemical, antioxidant, molecular, and cell levels.

Dapagliflozin, Liraglutide, and Their Combination Attenuate Diabetes Mellitus-Associated Hepato-Renal Injury-Insight into Oxidative Injury/Inflammation/Apoptosis Modulation.

In this study, we aim to explore the beneficial therapeutic impacts of dapagliflozin (Dapa), a highly potent, reversible, and selective sodium–glucose cotransporter-2 inhibitor, and liraglutide (Lira), a glucagon-like peptide-1 (GLP-1) receptor agonist, as hypoglycaemic agents for the management of diabetes mellitus (DM), as well as their combination against DM-induced complications, including hepato-renal injury. Indeed, the progression of DM was found to be associated with significant hepatic and renal injury, as confirmed by the elevated biochemical indices of hepatic and renal functions, as well as histopathological examination. Dapa, Lira, and their combination effectively attenuated DM-induced hepatic and renal injury, as confirmed by the recovery of hepatic and renal functional biomarkers. The administration of both drugs significantly reduced the tissue contents of MDA and restored the contents of GSH and catalase activity. Moreover, NF-κB and TNF-α expression at the protein and gene levels was significantly reduced in the liver and the kidney. This was in parallel with the significant reduction in the caspase-3 content in the liver and the kidney, as well as suppressed cleaved caspase-3 expression in the hepatic and renal specimens, as confirmed by immune–histochemical analysis. Notably, the combined Dapa/Lira treatment demonstrated an additive superior hepato-renal protective impact compared with the use of either drug alone. Thus, it appears that Dapa and Lira, through the coordinated modulation of oxidative, inflammatory, and apoptotic signalling, confer a significant hepato-renal protective impact against DM-induced complications and tissue injury.

Pergularia daemia (Apocynaceae) mitigates rifampicin-induced hepato-renal injury: potentials in the management of liver and kidney diseases

Medicinal potentials of Pergularia daemia leaves in managing hepato-renal toxicity induced by rifampicin were investigated. Twenty-five (25) Wistar rats were randomly placed into five groups containing five animals each. All the animals, except group I, were orally exposed to 250 g/kg bwt rifampicin and administered different treatments. Specific liver and kidney biomarkers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were determined. In addition, malondialdehyde (MDA), lipid profile, superoxide dismutase (SOD), catalase (CAT), as well as reduced glutathione (GSH) were determined in the serum, liver, and kidney homogenates of experimental animals. Results indicate that exposure to rifampicin caused significant depletion in SOD and CAT relative to the control animals. Lipid profile was deranged, while ALT, AST, ALP, urea, uric acid, bilirubin, creatine kinase, and MDA level were elevated by rifampicin exposure. All deranged biochemical indices, as well as distorted histoarchitecture, were restored dose-dependently after treatment with P. daemia. In conclusion, P. daemia ameliorated rifampicin toxicity on the liver and kidney as indicated in the restoration of all deranged biochemical and histopathological indices measured. Hence, it is a potential therapeutic agent that can be harnessed as the panacea to the menace of liver and kidney diseases.

Apigeninidin-rich Sorghum bicolor (L. Moench) extracts suppress A549 cells proliferation and ameliorate toxicity of aflatoxin B1-mediated liver and kidney derangement in rats.

Sorghum bicolor plant has a high abundance of 3-deoxyanthocyanins, flavonoids and other polyphenol compounds that have been shown to offer numerous health benefits. Epidemiological studies have linked increased intake of S. bicolor to reduced risk of certain cancer types, including lung adenocarcinoma. S. bicolor extracts have shown beneficial effects in managing hepatorenal injuries. This study investigated the cytotoxic potential of three apigeninidin-rich extracts of S. bicolor (SBE-05, SBE-06 and SBE-07) against selected cancer cell lines and their ameliorative effect on aflatoxin B1 (AFB1)-mediated hepatorenal derangements in rats. We observed that, among the three potent extracts, SBE-06 more potently and selectively suppressed the growth of lung adenocarcinoma cell line (A549) (IC50 = 6.5 μg/mL). SBE-06 suppressed the expression of STAT3 but increased the expression of caspase 3. In addition, SBE-05, SBE-06 and SBE-07 inhibited oxidative and nitrosative stress, inflammation, and apoptosis and preserved the histoarchitectural networks of the liver and kidney of rats treated with AFB1. These in vitro and in vivo studies indicate the potential of these cheap and readily accessible extracts for cancer therapy and as chemo-preventive agents in preventing aflatoxin-related health issues.

Melatonin and zinc supplements with physical and mental activities subside neurodegeneration and hepatorenal injury induced by aluminum chloride in rats: Inclusion of GSK-3β-Wnt/β-catenin signaling pathway

Alzheimer's disease (AD) is an irreversible, progressive cognitive dysfunction. Inflammaging is the greatest common factor between AD and hepatorenal malfunction. This study aimed to use melatonin (MEL) and zinc sulfate (Zn) in addition to physical and mental activities (PMA) to ameliorate AlCl3-induced AD as well as investigate their impact on the associated hepatorenal impairment. MethodsSeven groups of rats each received: saline (control group), AlCl3 (70 mg/kg, i.p.), PMA, either alone or with a combination of Mel (10 mg/kg, p.o) and/or Zn (16 mg/kg, p.o). Neurological deterioration was assessed after 5 weeks using behavioral tests, histopathological examination, and measurements of acetylcholinesterase (ACHE), brain monoamines, oxidative stress, and inflammatory markers, Amyloid precursor protein (APP), amyloid-β (Aβ), tau levels, and brain derived neurotrophic factor (BDNF). Moreover, the GSK-3β-Wnt/β-catenin signaling pathway was assessed. Additionally, oxidative stress and inflammatory markers were determined in liver and kidney tissues with concurrent evaluation of hepatic and renal functions. ResultsThe histopathological examination revealed a cerebral cortex and hippocampus deterioration in the AD group with a decline in spatial learning and memory, besides a significant increase in AD markers in the brain and disturbance in GSK-3β-Wnt/β-catenin signaling. The AD group showed hepatorenal injuries supported by elevated oxidative stress and inflammatory markers. However, adding Mel and Zn to PMA significantly attenuated the neurodegeneration and enhanced hepatic and renal functions by ameliorating oxidant and inflammatory markers. ConclusionsCombining Mel and Zn supplements with PMA defends against AlCl3-induced AD by modulating GSK-3β-Wnt/β-catenin signaling and palliates the associated hepatorenal dysfunction.

Rejuvenating potentials of Curcuma longa on Sudan IV dye induced hepato-renal injury

Objectives: Sudan IV dye (S4D), has been reported to enhance the color of food products example palm oil, despite the health issues associated with these colorants. The potent antioxidant attribute of Curcuma longa facilitates its capacity to protect the kidney against deleterious attacks by free radicals. This study investigated the rejuvenating potentials of the extract of C. longa by S4D induced hepato-renal injury in rats. Material and Methods: Twenty-five female albino rats were distributed into five groups, as follows: Group 1 received distilled water and diet only, Group 2 received 10% S4D+100 mg C.L, Group 3 received 15% S4D +100 mg C.L, while Groups 4 and 5 received 200 mg and 250 mg C.L, respectively. After 3 weeks of administration of Curcuma treatment, animals were sacrificed; liver, kidney, and small intestine were collected for analyses. Aspartate and alanine aminotransferases, gamma-glutamyl transferase, glutathione-s-transferase, alkaline phosphatase, and lactate dehydrogenase, as well as some selected electrolytes were measured. Results: Results show that treatment with 200 mg and 250 mg/kg significantly (P < 0.05) rejuvenated these enzyme biomarkers while modulating the physiological levels of the serum electrolytes and kidney markers. Conclusion: C. longa exhibited a significant antioxidant potential that sustain the cells from the effect of S4D toxicity. Hence, the results indicate a possible ameliorative mechanism of the plant extract against S4D- induced hepato-renal injury. Therefore, the inclusion of C. longa into our daily diet might limit the effect of the hepato-renal injury.

Gastroprotective, hepatoprotective, and nephroprotective effects of thymol against the adverse effects of acetylsalicylic acid in rats: Biochemical and histopathological studies

Acetylsalicylic acid (Aspirin) has been used for a long time as an antipyretic and analgesic. Nevertheless, aspirin use is associated with severe morbidity and death because of its detrimental impacts on several organs, including the liver, kidneys, and stomach. The current investigation sought to ascertain the influence of thymol in mitigating aspirin-mediated gastric and hepato-renal injury. This was done by 1) evaluating gastric juice volume and pH as well as pepsin and prostaglandin E2 level; 2) measuring serum biochemical parameters and proinflammatory cytokines; 3) determining tissue oxidant/antioxidant status, and 4) identifying a link with gastric, hepatic and renal histopathological changes. Forty-eight rats were segregated to six groups: normal control, Th100, Th200, ASA, Th100 + ASA, Th200 + ASA. Daily administration of aspirin (ASA, 150 mg/kg body weight) for 3 successive days induced a significant increase in gastric juice volume, pepsin activity, serum transaminases, alkaline phosphatase, urea, creatinine, tumor necrosis factor-α, myeloperoxidase, and tissue malondialdehyde levels. In contrast, a significant reduction in gastric pH, prostaglandin E2, tissue non-enzymatic antioxidant (glutathione), and enzymatic antioxidant (superoxide dismutase, glutathione peroxidase, and catalase) levels. These biochemical changes were accompanied by histological modifications that included changes to the normal gastric, hepatic, and renal architectures. Pretreatment and simultaneous oral treatment with thymol (100 or 200 mg/kg body weight) plus ASA significantly improved all biochemical and histological changes in a dose-dependent way. Thymol's antiinflammatory and antioxidative properties may contribute to its protective action. As a result, thymol may represent a promising medication for preventing aspirin-induced gastric, liver, and renal damage.

Spirulina and C-phycocyanin mitigate titanium dioxide nanoparticle-induced hematobiochemical and hepatorenal disorders through antioxidative pathway

The present investigation is designed to evaluate the ameliorative efficacy of spirulina and its active constituent, C-phycocyanin, on hepatorenal injury induced by titanium dioxide nanoparticles (TiO2 NPs). Forty-eight male albino rats were randomly divided into six groups: control group, Spirulina treated group, C-phycocyanin treated group, TiO2 NPs treated group, TiO2 NPs+ Spirulina treated group and TiO2 NPs+ C-phycocyanin treated group. The estimation of hepatic and renal function markers and oxidative status as well as histopathologic alterations in hepatic and renal tissues were analyzed. Spirulina and C- phycocyanin treatments caused significant improvement in all hematological indices such as RBCs, Hb, HCT, and total and differential WBCs relative to the untreated TiO2 NPs group. Also, spirulina and C-phycocyanin treatments significantly alleviated hepatic enzymes and bilirubin concentrations. Oral administration of spirulina and C- phycocyanin decreased total cholesterol and triglycerides content significantly. Both Spirulina and C- phycocyanin attenuated creatinine, urea, and uric acid significantly. Furthermore, the present study revealed that spirulina and C- phycocyanin significantly increased hepatorenal antioxidants content and retard malondialdehyde (MDA) formation. Histopathological examinations displayed that both spirulina and C- phycocyanin treatments repaired mostly the abnormal architecture of hepatic and renal tissues induced by TiO2 NPs. In conclusion, the modulatory role of spirulina and C-phycocyanin may be due to their strong antioxidative effects and other active constituents of spirulina.

Lactobacillus rhamnosus Encapsulated in Alginate/Chitosan Microgels Manipulates the Gut Microbiome to Ameliorate Salt-Induced Hepatorenal Injury.

As the essential regulator of intestinal bacterial diversity, probiotics are a potential treatment for chronic high-salt diet (HSD)–induced metabolic dysfunction. Probiotic cells entrapped in microgels have been confirmed as being more effective than free cells in protecting bacteria against unfavorable conditions, that is, enhancing their stress resistance. This study explored the physiological mechanism by which probiotic microgels relieve HSD–induced hepatorenal injury. Herein, Lactobacillus rhamnosus was encapsulated in alginate-chitosan microgels which the percentage of alginate/chitosan was applied 1.5:0.5 (w/w) in this system, and the encapsulation significantly improved the probiotic viability in simulated gastrointestinal conditions. Mice were fed an HSD with L. rhamnosus (SDL) or L. rhamnosus microgels (SDEL). After 8 weeks of administration, dietary sodium was confirmed as inducing the hepatic and renal damages in mice, based on indicators, including serum biomarker levels, histopathological features of tissues, and pro-inflammatory cytokine contents in blood levels. However, the serum levels of urea nitrogen, creatinine, uric acid, glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, and alkaline phosphatase in the SDL and SDEL-fed mice were significantly lowered compared to the HSD-fed mice, especially in the SDEL group. HSD increased the abundances of Anaeroplasma, Enterorhabdus, Parvibacter, and Bacteroides, while the microgels increased the abundances of Lactobacillus, Bifidobacterium, Mucispirillum, and Faecalibaculum. Significant variations of fecal metabolome were validated for SDEL-treated mice, containing those linked to entero-hepatic circulation (e.g., cholic acid), carbohydrate metabolism (i.e., L-lactic acid), and increased antioxidants including citric acid. Furthermore, the probiotic microgels ameliorated intestinal damage by improving barrier and absorption functions. These results augmented existing knowledge on probiotic application for salt toxicity.

Safety and efficacy of terlipressin in acute-on-chronic liver failure with hepatorenal syndrome-acute kidney injury (HRS-AKI): a prospective cohort study

Terlipressin with albumin, the recommended treatment for hepatorenal syndrome-acute kidney injury (HRS-AKI), is associated with adverse events. Furthermore, the course of AKI in patients with acute-on-chronic liver failure (ACLF) is unknown. We aimed to analyze the safety and efficacy of terlipressin infusion and AKI course in patients with ACLF. We prospectively enrolled consecutive adult patients with ACLF with HRS-AKI (satisfying EASL criteria) treated with terlipressin infusion between 14 October 2019 and 24 July 2020. The objectives were to assess the incidence of adverse events, response to terlipressin, course of HRS-AKI and predictors of mortality. A total of 116 patients were included. Twenty-one percent of patients developed adverse effects. Only 1/3rd of patients who developed adverse events were alive at day 90. Sixty-five percent of the patients responded to terlipressin. Nearly 22% developed recurrence of HRS, and 5.2% progressed to HRS-chronic kidney disease. TFS was 70.4% at day 30 and 57.8% at day 90. On multivariate stepwise Cox regression analysis terlipressin non-response (hazard ratio [HR], 3.49 [1.85–6.57]; P < 0.001) and MELD NA score (HR,1.12 [1.06–1.18]; P < 0.001) predicted mortality at day-90. Patients with ACLF who develop terlipressin related adverse events have dismal prognoses. Terlipressin non-response predicts mortality in patients with ACLF and HRS-AKI.

Calcium dobesilate protects against d-galactose-induced hepatic and renal dysfunction, oxidative stress, and pathological damage.

Calcium dobesilate (CaD) is used for the treatment of diabetic retinopathy and nephropathy. This agent exerts antioxidant effects. In the present study, we evaluated the protective effects of oral administration of CaD against hepatorenal damages in a mice model of aging induced by d-galactose (d-gal). We used 28 male albino mice, which equally and randomly were divided into four groups as follows: intact, aging (d-gal at the dose of 500 mg/kg, p.o.), aging + CaD 50 (d-gal plus CaD at the dose of 50 mg/kg), and aging + CaD 100 (d-gal plus CaD at the dose of 100 mg/kg, p.o.). All drugs were administered orally once a day for 42 days. The liver and kidney damages were evaluated by measuring mass indices, levels of serum creatinine and blood urea nitrogen, and activities of serum alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase and by histopathological evaluation. Moreover, hepatic and renal tissue oxidant/antioxidant markers (malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase) were measured. The results showed that d-gal treatment induced significant oxidative stress in the kidney and liver that was paralleled by dysfunctions and histological alterations of these organs. CaD significantly improved the liver and kidney indices, implemented functional capacity of the liver and kidney, as well as decreased oxidative stress enhancing antioxidative enzyme activities. CaD treatment also inhibited the development of histological alterations of both kidney and liver. CaD might represent a promising therapeutic agent for the attenuation of hepatorenal injuries induced by aging.

The Pivotal role of Cerium oxide nanoparticles in thioacetamide-induced hepatorenal injury in rat.

The Pivotal role of Cerium oxide nanoparticles in thioacetamide-induced hepatorenal injury in rat.

Administration of Costus igneus Nak leaf extract improves diabetic-induced impairment in hepatorenal functions in male albino rats

ObjectivesThe present study was designed to evaluate the therapeutic efficacy Costus igneus Nak leaf extract against the diabetes-induced hepatorenal injury in rats. MethodsDiabetes was induced in male albino rats by administering single injection of streptozotocin (55 mg/kg) for one day. The diabetic condition was established by estimation of blood glucose level; animals with blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into seven experimental groups, viz group I served as the control, group II-CI-300mg/Kg (per se), group III-Diabetic, group IV-diabetic+CI (100mg/kg), group V-diabetic+CI (200mg/kg), group VI-Diabetic+CI (300 mg/kg) and group VII-diabetic+glibenclamide (0.5mg/kg). Treatment regimens were started 24 h after the confirmation of the successful induction of diabetes and continued for four consecutive weeks at three doses (100–300 mg/kg). After the completion of experimental period animals were sacrificed, blood was collected through retro-orbital puncture for separation of serum for assessment of liver (ALT, AST, ALP, albumin, globulin and bilirubin) and kidney-specific biomarkers (creatinine, urea, and uric acid, Na+ and K+), and inflammatory cytokines (TNF-α, IL-6, IL-1β, TGF-β1, IL-10. Liver and kidneys were harvested for histopathology and biochemical screening. Hepatorenal protective activity was evaluated by estimating different biochemical variables and histopathology by hematoxylin and eosin staining of the liver and kidney tissues. Results and ConclusionsThree different daily doses of the plant extract showed recovery in all the biochemical parameters such as lipid peroxidation, reduced glutathione, superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase, glutathione reductase, glutathione peroxidase, and glutathione-S-transferase; ALT, AST, and ALP; creatinine, urea, and uric acid; total cellular protein content in tissues, glycogen content, and serum protein content (albumin and globulin); and inflammatory cytokines. However, significantly higher recovery was observed in the 300 mg/kg dose treated group of animals. Considerations of the serological, biochemical and histopathological studies, it may be concluded that that the C. igneus Nak leaf extract abolished various deleterious effects of type 1 diabetes induced hepatorenal functions.

Going Micro in Leptospirosis Kidney Disease.

Leptospirosis is a zoonotic and waterborne disease worldwide. It is a neglected infectious disease caused by Leptospira spp., as well as a reemerging disease and global public health problem with respect to morbidity and mortality both in humans and animals. Leptospirosis emerges as a leading cause of acute febrile illness along with hepatorenal injury in many countries, including Thailand. While most affected persons are symptomatic in acute disease, which is always difficult to differentiate from other tropical diseases, there is growing evidence of subtle manifestations that cause unrecognized chronic symptoms. The kidney is one of the common organs affected by Leptospires. Although acute kidney injury in the spectrum of interstitial nephritis is a well-described characteristic in severe leptospirosis, chronic kidney disease from leptospirosis is widely discussed. Early recognition of severe leptospirosis leads to reduce morbidity and mortality. Thus, in this review, we highlight the spectrum of characteristics involved in leptospirosis kidney disease and the use of serologic and molecular methods, as well as the treatments of severe leptospirosis.

Ameliorative impacts of chrysin against gibberellic acid-induced liver and kidney damage through the regulation of antioxidants, oxidative stress, inflammatory cytokines, and apoptosis biomarkers.

Gibberellic acid (GA3), a widely known plant growth regulator, has been mostly used in agriculture. Little is known regarding its toxicity or the impact of its metabolic mechanism on human health. The current study examined the protective impact of chrysin against GA3-induced liver and kidney dysfunctions at biochemical, molecular, and histopathological levels. Forty male albino rats were allocated into 4 groups. The control group received saline; the chrysin group received 50mg/kg/BW orally daily for 4 weeks; the GA3 group received 55mg/kg/BW GA3 via daily oral gavage for 4 weeks, and the protective group (chrysin + GA3) was administered both chrysin and GA3 at the same dosage given in chrysin and GA3 groups. Chrysin was administered 1 h earlier than GA3. The GA3 induced liver and kidney injuries as proven by the elevation of hepatic and renal markers with a significant increase in malondialdehyde levels. Furthermore, a decrease of catalase and glutathione was reported in the GA3-administered rats. Pre-administration of chrysin significantly protected the hepatorenal tissue against the deleterious effects of GA3. Chrysin restored the hepatorenal functions and their antioxidant ability to normal levels. Moreover, chrysin modulated the hepatorenal toxic effects of GA3 at the molecular level via the upregulation of the antiapoptotic genes, interleukin-10 (IL-10), hemoxygenase-1, and nuclear factor erythroid 2-related factor 2 expressions; the downregulation of the kidney injury molecule-1 and caspase-3 mRNA expressions; and a decrease in IL-1β and tumor necrosis factor-α secretions. Additionally, the pre-administration of chrysin effectively attenuated the GA3-induced hepatorenal histopathological changes by regulating the immunoexpression of cytochrome P450 2E1 (CYP2E1) and pregnane X receptor, resulting in normal values at the cellular level. In conclusion, chrysin attenuated GA3-induced oxidative hepatorenal injury by inhibiting free-radical production and cytokine expression as well as by modulating the antioxidant, apoptotic, and antiapoptotic activities. Chrysin is a potent hepatorenal protective agent to antagonize oxidative stress induced by GA3.

Calcium dobesilate ameliorates hepatorenal injury induced by carbon tetrachloride in mice.

Objective(s):Calcium dobesilate (CaD) has anti-oxidant, anti-inflammatory, and anti-apoptotic effects. In this study, the protective effects of CaD against hepatorenal damage induced by carbon tetrachloride (CCl4) in mice were evaluated. Materials and Methods:Thirty male mice were randomly divided into five groups: Control, CaD 100 mg/kg, CCl4, CCl4+CaD 50 mg/kg, and CCl4+CaD 100 mg/kg. CaD (50 and 100 mg/kg) was administered orally once a day for 4 weeks. The liver and kidney indices (serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase levels) were determined. Also, liver and kidney tissue oxidant/anti-oxidant markers (glutathione peroxidase, malondialdehyde, total anti-oxidant capacity, and superoxide dismutase) were measured. Cleaved caspase-3, Bax, cytochrome-c, and Bcl-2 protein levels were measured by immunoblotting method in the liver and kidney tissues. The liver and kidney histopathological changes were evaluated by the Hematoxylin and Eosin (H&E) staining method.Results:CCl4 induced significant oxidative stress and apoptosis in kidney and liver tissues that was concomitant with histopathological abnormalities in these organs in the CCl4 group versus the control (P<0.05). However, CaD (100 mg/kg) could significantly improve the histopathological change in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05). In addition, CaD (100 mg/kg) attenuated the pro and anti-apoptotic markers in the liver and kidney tissues of CCl4+CaD 100 mg/kg mice versus the CCl4 group (P<0.05).Conclusion:CaD (100 mg/kg) has a protective effect against hepatorenal injury induced by CCl4 at least via its anti-apoptotic and anti-oxidant properties.

N-Acetylcysteine Alleviated the Deltamethrin-Induced Oxidative Cascade and Apoptosis in Liver and Kidney Tissues.

Deltamethrin (DLM) is a synthetic pyrethroid with anti-acaricide and insecticidal properties. It is commonly used in agriculture and veterinary medicine. Humans and animals are exposed to DLM through the ingestion of polluted food and water, resulting in severe health issues. N-acetylcysteine (NAC) is a prodrug of L-cysteine, the precursor to glutathione. It can restore the oxidant-antioxidant balance. Therefore, this research aimed to examine whether NAC may protect broiler chickens against oxidative stress, at the level of biochemical and molecular alterations caused by DLM intoxication. The indicators of liver and kidney injury in the serum of DLM-intoxicated and NAC-treated groups were examined. Furthermore, lipid peroxidation, antioxidant markers, superoxide dismutase activity, and apoptotic gene expressions (caspase-3 and Bcl-2) were investigated. All parameters were significantly altered in the DLM-intoxicated group, suggesting that DLM could induce oxidative damage and apoptosis in hepato-renal tissue. The majority of the changes in the studied parameters were reversed when NAC therapy was used. In conclusion, by virtue of its antioxidant and antiapoptotic properties, NAC enabled the provision of significant protection effects against DLM-induced hepato-renal injury.

Anserine beneficial effects in hyperuricemic rats by inhibiting XOD, regulating uric acid transporter and repairing hepatorenal injury.

This study aims to investigate the anti-hyperuricemia effect and mechanism of anserine in hyperuricemic rats. Hyperuricemic rats were induced with a combination of 750 mg per kg bw d potassium oxazinate (PO) and 200 mg per kg bw d hypoxanthine for a week, and the rats were separately orally administered anserine (20, 40, 80 mg kg-1) and allopurinol (10 mg kg-1) for three weeks. The results show that the content of serum uric acid (SUA) decreased by approximately 40% and 60% after the intervention of anserine and allopurinol, respectively. The activity of superoxide dismutase (SOD) was increased and the levels of malondialdehyde (MDA), alkaline phosphatase (ALP) and alanine aminotransferase (ALT) were significantly decreased in the anserine groups. After the administration of anserine, the contents of blood urea nitrogen (BUN) and creatinine (Cr) were reduced in the kidney, and the levels of the proinflammatory cytokines IL-1β, IL-6β, TNF-α and TGF-β and inflammatory cell infiltration were reduced in both the liver and kidney. Moreover, the gene expressions of xanthine oxidase (XOD), renal urate transporter 1 (URAT1) and glucose transporter type 9 (GLUT9) were downregulated by anserine administration, and the gene expressions of ATP-binding cassette transporter G2 (ABCG2), organic anion transporter 1 (OAT1) and organic anion transporter 3 (OAT3) were upregulated at the same time. These findings suggest that hepatorenal injury was repaired by anserine, which further regulated the expression of hepatic XOD and renal URAT1, GLUT9, ABCG2, OAT1 and OAT3 to relieve hyperuricemia in rats.

Ameliorative efficacy of Sepia officinalis ink extract on hepatorenal injury-induced following high-dose folic acid supplementation in rats

Sepia ink, a black suspension of melanin granules, is a multifunctional marine bioactive material. The present study aims to evaluate the ameliorative effect of the ink extract (IE) of the cuttlefish (Sepia officinalis) during high dosage administration of the FA in rats. Kidney injury induced by a single oral dose of FA (250 mg /kg). Eighteen male Wistar albino rats were the control, FA group, and FA+ IE group (250mg/kg). The IE showed a significant ameliorative effect against hepatorenal injury induced by high intake of FA as evident by decreasing the levels of serum aminotransferases (AST and ALT), urea, creatinine, uric acid, and significantly increased total serum albumin. Treatment with IE normalized the antioxidant status of the injured animals by reducing the MDA and the significant increase in the levels of GSH and CAT. The present study revealed that IE had an insightful effect against hepatorenal injury-induced following high intake of FA in rats, as it alleviates the alterations in the oxidative stress markers.