Hepatoprotective and Nephroprotective Effects of Empagliflozin and Ethanolic-leaf extract of Mentha piperita against Aluminium chloride and D-galactose-Induced Oxidative Stress in the Liver and Kidney of Wistar Rats
Jul 2026· Magna Scientia Advanced Research and Reviews· 1 citation
TL;DR
ELMP and EMPG demonstrate potent hepatoprotective and nephroprotective effects through multi-target antioxidant mechanisms, supporting their therapeutic potential as integrated strategies for peripheral organ protection in aluminium-induced toxicity.
Abstract
Background: Aluminium chloride (AlCl3) and D-galactose induce systemic oxidative toxicity with documented accumulation in the liver and kidney. This study evaluated the hepatoprotective and nephroprotective effects of empagliflozin (EMPG) and ethanolic leaf extract of Mentha piperita (ELMP) against AlCl3 and D-galactose-induced oxidative stress in liver and kidney tissues of male Wistar rats.
Methods: Thirty-six male Wistar rats were divided into six groups (n=6): normal control (A), disease control (B: AlCl3 150 mg/kg plus D-galactose 50 mg/kg for 6 weeks), and four treated groups (C and D: ELMP 200 or 400 mg/kg; E: EMPG 10 mg/kg; F: ELMP 400 mg/kg plus EMPG 10 mg/kg) given for 4 weeks alongside AlCl3 and D-galactose. Tissues were assayed for malondialdehyde (MDA), superoxide dismutase (SOD), reduced glutathione (GSH), and catalase. Data were analysed by one-way ANOVA with post hoc LSD comparison at p less than or equal to 0.05.
Results: Group B showed significantly elevated hepatic and renal MDA alongside severely depleted SOD, GSH, and catalase compared to Group A. ELMP produced dose-dependent restoration of antioxidant enzymes. Group F achieved the most complete restoration, approaching normal control values in both organs. F-ratios confirmed significant overall group differences across all parameters (kidney MDA: 56.125; liver MDA: 49.366).
Conclusion: AlCl3 and D-galactose induce significant hepatic and renal oxidative stress. ELMP and EMPG, particularly in combination, demonstrate potent hepatoprotective and nephroprotective effects through multi-target antioxidant mechanisms, supporting their therapeutic potential as integrated strategies for peripheral organ protection in aluminium-induced toxicity.
It is indicated that combining papaya, neem, and garlic extracts may provide greater hepatoprotection than administering the individual extracts against DEN-induced liver injury, and supports further mechanistic and preclinical evaluation of this polyherbal formulation before its potential therapeutic application in liver-disease management.
Egeonu Us, Umaru Ij, Izam Ed et al.· African Journal of Clinical...· 0 citations
Objective: The objective of the study is to evaluate the nephroprotective potential of Zanthoxylum armatum bark extract Methanolic extract of Zanthoxylum armatum (MZA) against cisplatin (CP)-induced nephrotoxicity in experimental rats.
Methods: Wistar albino rats, weighing between 150 and 200 g, were split into five groups: Normal saline, intraperitoneally CS 16 mg/kg once, and oral methanolic extract of Z. armatum bark at 100, 200, and 400 mg/kg for 42 days. Analyses of serum creatinine, blood urea, blood urea nitrogen, lipid peroxidation (LPO), uric acid, renal enzymatic and non-enzymatic antioxidants, and kidney histopathology were carried out.
Results: Electrolyte imbalance, elevated renal biomarkers, decreased antioxidant enzyme activity, and increased LPO all showed that CS significantly impaired the kidneys and produced oxidative stress (p<0.001). Over 42 days, treatment with the methanolic extract considerably and dose-dependently reduced these changes, restoring renal function indicators, electrolyte balance, and antioxidant status, demonstrating the extract’s strong nephroprotective and antioxidant efficacy.
Conclusion: These results substantiate the ethnomedical usage of Z. armatum bark extract by providing strong evidence that it functions as a powerful scavenger of free radicals and counteracts the harmful effects of CS in both histological and biochemical parameters.
PALLAVI GHILDIYAL, NEERAJ KUMAR, ALOK BHATT et al.· Asian Journal of Pharmaceuti...· 0 citations
Aim: Acetaminophen overdose has been associated with liver and kidney failure. This study aimed to evaluate the ameliorative effects of Flueggea virosa on the liver and kidneys in acetaminophen-induced toxicity.
Study Design: Original Paper.
Place and Duration of Study: Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, University of Ibadan, from March 2026 to May 2026.
Methodology: The methanol fraction of Flueggea virosa (FVMF) was obtained from the hydroethanolic leaf extract. Twenty-five Wistar rats were allocated to five groups of five rats each. Group 1 received distilled water, whereas Groups 2–5 received acetaminophen (1000 mg/kg) on days 1 and 2. Groups 3–5 subsequently received FVMF at 300, 150, and 75 mg/kg, respectively, by oral administration until day 10. Serum samples were obtained, and organs were collected for weighing and histopathological examination on day 11.
Results: No significant reduction was observed in any biochemical parameter (P > 0.05) at the three doses of FVMF, except for ALP (P < 0.05). A slight reduction in BUN (P = 0.337) and no renal lesion were observed at 300 mg/kg; the other doses were associated with lesions in the liver, kidney, and spleen. The measured antioxidant activity of FVMF was higher in the DPPH assay than in the FRAP assay.
Conclusion: Acetaminophen induced liver and kidney toxicity. At the tested doses (300, 150, and 75 mg/kg), FVMF did not ameliorate this toxicity, as no significant reductions in the biochemical parameters were observed between the treated groups and the acetaminophen-only group. Lesions were observed in the examined organs, including the spleen. Under the present experimental conditions, FVMF was not supported as a candidate for managing hepatorenal injury; its reported cytotoxic and anticancer activities require separate evaluation.
Okwulu O. J., R. A. Oguntoye, I. Lawal et al.· International Journal of Bio...· 0 citations
Potassium bromate (KBr) is a potent oxidizing agent that induces oxidative stress, inflammation, and hepatic injury. This study evaluated the protective effects of Solanum aethiopicum leaf extract against KBr-induced alterations in liver function and inflammatory cytokines in Wistar rats. Thirty Wistar rats (140–150 g) were randomly assigned to five groups (n = 6): normal control, KBr (50 mg/kg), KBr + S. aethiopicum extract (300 mg/kg), KBr + S. aethiopicum extract (600 mg/kg), and KBr + vitamin C (100 mg/kg). Potassium bromate was administered for two weeks before treatment with the extract or vitamin C. Serum liver function indices (total protein, albumin, globulin, ALT, AST, ALP, and total bilirubin) and inflammatory biomarkers (IL-1β and TNF-α) were determined using standard spectrophotometric methods. Data were analyzed using one-way ANOVA followed by Tukey’s post hoc test. Potassium bromate significantly disrupted liver function parameters and reduced (P < 0.05) IL-1β levels compared with the control, indicating hepatic dysfunction and impaired inflammatory homeostasis. Treatment with S. aethiopicum extract significantly restored IL-1β concentrations while maintaining TNF-α levels comparable to the control. The extract also ameliorated KBr-induced alterations in serum proteins and bilirubin. In conclusion, S. aethiopicum leaf extract protected against potassium bromate-induced hepatic dysfunction and inflammatory disturbances, supporting its potential as a natural hepatoprotective and immunomodulatory agent. Further studies are recommended to elucidate its underlying mechanisms of action.
Keywords: inflammation, interleukin-1β, tumor necrosis factor-α, potassium bromate, Solanum aethiopicum.
Okon Victoria Edem, Idam Benedict Umagu, I. Nnah· IAA Journal of Biological Sc...· 0 citations
Phenylhydrazine is a hydrazine derivative widely used experimentally to induce oxidative and haemolytic tissue injury in animal models. This study investigated the ameliorative effect of ethanolic extract of okra (Abelmoschus esculentus) leaves on phenylhydrazine-induced gastric toxicity in adult male Wistar rats. Twenty-five adult male Wistar rats (140-220 g) were randomly assigned into five groups of five animals each. Group A (control) received feed and distilled water ad libitum; Group B received phenylhydrazine only (40 mg/kg); Group C received ethanolic extract of A. esculentus only (100 mg/kg); Group D received phenylhydrazine (40 mg/kg) co-administered with the extract (100 mg/kg); and Group E received phenylhydrazine (40 mg/kg) co-administered with a higher dose of the extract (200 mg/kg). Administration was carried out daily by oral cannula for 21 days. Body weight, relative stomach weight, and gastric histoarchitecture were assessed at the end of the study. The median lethal dose (LD50) of the extract, determined by Lorke's method, exceeded 5000 mg/kg, indicating a wide margin of safety. Rats induced with phenylhydrazine alone (Group B) showed a non-significant reduction in body weight and relative stomach weight, alongside severe histological gastric ulceration with marked inflammatory cell infiltration of the submucosa. Co-administration of the extract with phenylhydrazine (Groups D and E) was associated with visibly reduced ulceration and progressively improved mucosal healing relative to Group B, with the higher extract dose (Group E) showing the more advanced histological recovery. These findings suggest that ethanolic extract of A. esculentus exerts a dose-related gastroprotective and ameliorative effect against phenylhydrazine-induced gastric injury, supporting its potential as a dietary adjunct in the management of oxidative gastric mucosal damage.
E. O. Nweke, Benedict Onyekachukwu Ekwuno, A. Obi et al.· IPS Journal of Basic and Cli...· 1 citation
Background: Lead toxicity is one of the most harmful heavy metal poisonings in humans and animals. It affects the kidneys’ ability to excrete waste and toxic substances, thereby causing oxidative stress, inflammation and kidney damage.
Aims: This study investigated the effects of ethanol leaf extract of Momordica balsamina on renal function parameters and oxidative markers in lead-induced nephrotoxic Wistar rats.
Methodology: Acute toxicity testing was conducted using Lorke’s (1983) method. Thirty (30) healthy adult Wistar rats, weighing 180–200 g and obtained from the Animal House of the Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University, Sokoto, were randomly divided into six (6) groups of five (5) rats each. Group I served as the normal control and received standard feed and water. Group II (negative control) received 50 mg/kg lead acetate only for 14 days. Group III (positive control) received 50 mg/kg lead acetate for 14 days and was then treated with 70 mg/kg silymarin for 28 days. Groups IV, V and VI received 50 mg/kg lead acetate for 14 days and were then treated with graded doses of ethanol leaf extract of Momordica balsamina (100, 200 and 400 mg/kg, respectively) for 28 days. At the end of the experimental period, blood samples were collected for biochemical analyses. The oxidative stress marker malondialdehyde (MDA), antioxidant enzymes (catalase and superoxide dismutase), and renal function parameters, including sodium, potassium, chloride, bicarbonate, urea and creatinine, were determined using standard laboratory methods.
Results: Lead acetate administration significantly increased serum MDA, sodium, potassium, chloride, urea and creatinine levels, with significant reductions in catalase, superoxide dismutase and bicarbonate levels when compared with the normal control. However, treatment with ethanol leaf extract of Momordica balsamina caused a significant decrease in lipid peroxidation, improved antioxidant enzyme activity and improved renal function parameters when compared with the negative control group.
Conclusion: The findings suggest that ethanol leaf extract of M. balsamina produced no visible toxic effect even at a dose of 5000 mg/kg body weight. The leaf extract of M. balsamina ameliorated oxidative stress and reduced the functional impact of lead toxicity on the kidneys by improving renal function.
N. Fakai, M. H. Yeldu, U. Wali et al.· Asian Journal of Biochemistr...· 0 citations