Nephrotoxicity In Male Albino Rats Research Articles

Empagliflozin mitigates methotrexate-induced nephrotoxicity in male albino rats: insights on the crosstalk of AMPK/Nrf2 signaling pathway

BackgroundThe anti-diabetic drug, empagliflozin (EMPA), has many pleiotropic actions and is challenged recently to possess renoprotective properties. This renoprotective potential is proposed to be mediated via the activation of AMP-activated protein kinase (AMPK)/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathways. This research investigated the renoprotective potential and the mechanistic pathway of EMPA against methotrexate (MTX)-induced nephrotoxicity and evaluated the role of AMPK by utilizing an AMPK inhibitor, dorsomorphin (Dorso).MethodsThirty male Wistar rats, weighing 180–200 g, were divided equally into five groups. Group I represented the control group. Nephrotoxicity was induced in the remaining rats through the administration of a single intraperitoneal injection of MTX (20 mg/kg). Rats were then randomly assigned to: Group 2 (received MTX injection only); Group 3 (received MTX and EMPA 30 mg/kg/day); Group 4 (received MTX and Dorso 0.2 mg/kg/day), Group 5 (received MTX, Dorso, EMPA). After one week, blood samples were collected, the rats were euthanized, and renal tissues were harvested for biochemical and histomorphometric assessments.ResultsMTX produced a significant rise in serum creatinine and tissue MDA levels; an increase in BAX, p53, cytochrome-c expression; a reduction in Bcl2 level; and disruption of renal microarchitecture. In contrast, EMPA therapy in group 3, resulted in a significant improvement of all these parameters, correlated with significant increase in AMPK phosphorylation and Nrf2 expression. Importantly, the co-administration of Dorso, in group 5, prevented EMPA’s beneficial effects.ConclusionEMPA has a potential protective effect against MTX-induced toxicity through the activation of the AMPK/Nrf2 signaling pathway.

Nephroprotective Roles of L-Cysteine, Silymarin and Ursodeoxycholic acid, against Carbon Tetrachloride induced Nephrotoxicity in Male Albino Rats

Nephroprotective Roles of L-Cysteine, Silymarin and Ursodeoxycholic acid, against Carbon Tetrachloride induced Nephrotoxicity in Male Albino Rats

Biochemical and Histopathological Assessment of Zinc Acetate-Induced Nephrotoxicity in Male Albino Rats

Biochemical and Histopathological Assessment of Zinc Acetate-Induced Nephrotoxicity in Male Albino Rats

Protective Effect of Chitosan and Chitosan Nanoparticles on Dioxin-Induced Haematotoxicity and Nephrotoxicity in Male Albino Rats

Protective Effect of Chitosan and Chitosan Nanoparticles on Dioxin-Induced Haematotoxicity and Nephrotoxicity in Male Albino Rats

Histological and biochemical study of the protective effects of Uncaria tomentosa versus L-arginine against fipronil-induced nephrotoxicity in male albino rats

Histological and biochemical study of the protective effects of Uncaria tomentosa versus L-arginine against fipronil-induced nephrotoxicity in male albino rats

Morphological, immunohistochemical, and biochemical study on the ameliorative effect of gallic acid against bisphenol A-induced nephrotoxicity in male albino rats

This study aimed to determine the effect of gallic acid (GA) on ameliorating bisphenol A (BPA) nephrotoxicity in male rat kidneys. Forty rats were assigned randomly into two groups: control (ten animals) and BPA (40 mg/kg bwt) (thirty animals), the second group was divided into three subgroups: BPA alone, BPA + G50 (50 mg/kg bwt), and BPA + G200 (200 mg/kg bwt). The biochemical analysis included measurements of the contents of nitric oxide, lipid peroxidation, reactive oxygen species, and cytokines (interleukin-1α and interleukin-6) in the kidney. The antioxidant enzymes catalase and superoxide dismutase were also measured in the kidney. Kidney function was assessed by determining uric acid, urea, and creatinine levels. The morphological investigations included hematoxylin and eosin staining for assessing the general histology and determining the glomerular and corpuscular areas, the tubular cell degeneration mean area, and the mean leukocyte infiltration area. Also, collagen fiber intensity and polysaccharide content were analyzed. Furthermore, immunohistochemical, morphometric, and ultrastructural studies were carried out. The results revealed morphological, immunohistochemical, and biochemical alterations in the kidney. Most of these changes showed a satisfactory improvement of kidney damage when BPA-administered rats were treated with GA at both doses. In conclusion, GA exhibited a strong protective effect against BPA-induced nephrotoxicity.

Toxicological effects of thimerosal on rat kidney: a histological and biochemical study.

Thimerosal is an organomercurial compound, which is used in the preparation of intramuscular immunoglobulin, antivenoms, tattoo inks, skin test antigens, nasal products, ophthalmic drops, and vaccines as a preservative. In most of animal species and humans, the kidney is one of the main sites for mercurial compounds deposition and target organs for toxicity. So, the current research was intended to assess the thimerosal induced nephrotoxicity in male rats. Twenty-four adult male albino rats were categorized into four groups. The first group was a control group. Rats of Group-II, Group-III, and Group-IV were administered with 0.5µg/kg, 10µg/kg, and 50µg/kg of thimerosal once a day, respectively. Thimerosal administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione reductase (GR), glutathione (GSH), and protein content while increased the thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) levels dose-dependently. Blood urea nitrogen (BUN), creatinine, urobilinogen, urinary proteins, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) levels were substantially increased. In contrast, urinary albumin and creatinine clearance was reduced dose-dependently in thimerosal treated groups. The results demonstrated that thimerosal significantly increased the inflammation indicators including nuclear factor kappaB (NF-κB), tumor necrosis factor-α (TNF-α), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities, DNA and histopathological damages dose-dependently. So, the present findings ascertained that thimerosal exerted nephrotoxicity in male albino rats.

A histological investigation of the influence of Naringin on acetaminophen-induced nephrotoxicity in male albino rats

A study was conducted to examine the protective effects of naringin (NRG) on renal tissues of rats, specifically against acetaminophen (ACN)-induced damage. Thirty-two male rats were included in the study, divided into four groups. The first group (group I) was administered 1 ml/kg of saline orally, serving as the control group. The second group received 2g/kg of ACN on the first day. The third group received a single oral dose of 2g/kg of ACN on the first day, followed by 40 mg/kg of oral NRG for eight consecutive days. Lastly, the fourth group was given a single oral dose of 2g/kg of ACN on the first day, followed by 80 mg/kg of oral NRG for eight days. The rats were then euthanized and their kidneys were removed after they had been anesthetized for blood collection. The ACN-induced renal damage was characterized by significant reductions in body weight, levels of superoxide dismutase (SOD), and catalase. Additionally, there were significant increases in kidney weight, serum creatinine, blood urea nitrogen, serum uric acid, malondialdehyde enzyme (MAD), and histopathological alterations. The study demonstrated that NRG treatment at doses of 40 and 80 mg/kg b.w. effectively reduced renal toxicity and oxidative damage induced by ACN. The effectiveness of these improvements was demonstrated by the noticeable increase in body weight, elevated levels of SOD and CAT, as well as the reduction in kidney weight, CR, BUN, SUA, and MAD levels. As a result of these findings, NRG is confirmed to have antioxidant properties and be capable of protecting rats from renal toxicity caused by ACN.

The potential protective effects of citrus bergamot extract against amikacin-induced nephrotoxicity in male albino rats

The potential protective effects of citrus bergamot extract against amikacin-induced nephrotoxicity in male albino rats

Nephroprotective Effect of Green Synthesised Gold Nanoparticles Using Bark Extract of Terminalia arjuna on Acetaminophen Induced Nephrotoxicity in Male Albino Rat

Green synthesised gold nanoparticles offer a great promise in biomedicine. An overdose of acetaminophen causes severe hepatotoxicity and nephrotoxicity. The development of nephroprotective drugs through eco-friendly production routes is a major challenge for current pharmacology. This study was undertaken to examine the therapeutic effects of green synthesised gold nanoparticles (AuNPs) using aqueous bark extract of Terminalia arjuna, on acetaminophen induced nephrotoxicity in male albino rats and also to select the most effective dose of AuNPs to protect from nephrotoxicity . Terminalia arjuna , is a herbal plant of high interest in Asian traditional medicine. The bark of this tree has been widely used in the preparation of ayurvedic formulations such as powerful cardiotonic, antioxidative, antiuremic and antimicrobial properties. In this study 36 experimental albino rats were taken and randomly divided into 6 groups. Group 1 served as normal control, Group 2 received acetaminophen intraperitoneally at concentration of 500mg /kg of body weight for 14 days and Groups 3,4,5,6 were co-administered with acetaminophen (500mg/kg/day) along with AuNPs at doses 55, 175, 550, 2000 µg/kg/day intraperitoneally for 14 days. After 14 days all animals were sacrificed for biochemical and histopathological studies. Among different experimental doses of AuNPs (55,175,550, 2000µg/kg/day), 175µg/kg/day showed more potent activity towards biochemical indices and histopathological studies. There was significant (p<0.05) increase in Urea, Creatinine, CRP and MDA levels but significant decrease in SOD, CAT and GSH activity in acetaminophen treated group, in comparison to control group but co-administration with AuNPs (175µg/kg/day) restored the activities of these biochemical markers and also of the antioxidant enzymes. Hence,this study confirmed that AuNPs at dose 175µg/kg/day have better nephroprotective efficacy.

ABHRAK BHASMA AND SIO2 INFLUENCED MOBILITY OF LIPIDS IN LIVER AND KIDNEY OF CCL4 INDUCED ACUTELY INTOXICATED ALBINO RAT

In our earlier studies on CCl4 induced acute toxicity model (CCl4 3ml/kg body wt). Abhrak bhasma protects fatty degeneration of liver and associated nephrotoxicity in male albino rats. It had shown to function through production and management of free radicals (Teli and Kanase, 2020a, b). To study further the paths of Abhrak Bhasma mediated protection of acute hepatotoxicity and associated nephrotoxicity, liver, kidney and serum lipid contents were studied in present work. It shows no lipid accumulation in liver or kidney of normal rats by Abhrak Bhasma (10, 20, 30 and 40mg doses). But a same dose of silica in pure form (SiO2) is hepato and nephrotoxic in high doses in normal male albino rat. In acutely intoxicated rat also all the doses of Abhrak Bhasma influenced lipid contents of liver, kidney and serum show the protection of liver from fatty degeneration and also associated nephrotoxicity. Doses 30 and 40mg normalized the contents from liver, kidney and serum. The results are discussed to reveals the probable mode of action of Abhrak Bhasma.

Ameliorative Effect of Cerium Oxide Nanoparticles against Cadmium Nephrotoxicity in Male Albino Rats

Ameliorative Effect of Cerium Oxide Nanoparticles against Cadmium Nephrotoxicity in Male Albino Rats

Vitexin attenuates cisplatin-induced renal toxicity by reducing oxidative stress and inflammation

Cisplatin (CP) is one of the most effective chemotherapeutic drugs used to treat different tumors. Vitexin (VIT) is a natural flavonoid having various pharmacological activities along with its curative effects. The present research was planned to evaluate the therapeutic potential of VIT on cisplatin-induced renal damage in male albino rats. Twenty-four male albino rats were divided into four equal groups. These groups were treated with CP (10 mg/kg injection on the first day of trial) administered group, cotreated (CP; 10 mg/kg + VIT; 10 mg/kg) and only VIT (10 mg/kg orally till the end of the trial) treated group and a control. CP administration significantly decreased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), glutathione S-transferase (GST), glutathione (GSH), and glutathione reductase (GSR). The levels of thiobarbituric acid reactive substances (TBARS) and hydrogen peroxide (H2O2) were increased. CP-treatment significantly increased the levels of urea, creatinine, kidney injury molecule-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) while considerably reducing the creatinine clearance. The results demonstrated that CP significantly increased the inflammation markers, including tumor necrosis factor-α (TNF-α), nuclear factor kappa B (NF-κB), Interleukin-1β (IL-1β), Interleukin-6 (IL-6) levels and cyclooxygenase-2 (COX-2) activities and histopathological damages. However, co-treatment with VIT efficiently minimized the CP-induced biochemical, inflammatory, and histopathological impairments in rat kidneys. The study's outcomes indicated the significant curative efficacy of VIT to overcome CP-induced nephrotoxicity in male albino rats.

Potential Ameliorative Effects of L-Carnitine on Imidacloprid-Induced Hepato- and Nephrotoxicity in Male Albino Rats

The current study was intended to evaluate the possible protective role of L-Carnitine (LC) against imidacloprid (IM)-induced hepato- and nephrotoxicity in male albino rats. Thirty male albino rats were divided into 6 groups (n=5); control group, IM (32 mg/kg BW, 1/10 LD50)-treated group, LC200 (200 mg/kg BW)-treated group, LC400 (400 mg/kg BW)-treated group, IM+LC200-treated group, and IM+LC400-treated group. All treatments were given by oral route once daily for four weeks. Hematologically, the results exhibited that IM administration induced a significant decrease in red blood cells (RBCs) count, hemoglobin (Hb) and hematocrit (Ht) values. The erythrocytic indices (MCV, MCH and MCHC) displayed non-significant change in all treated groups. However, IM-treated group showed a significant leukocytosis and thrombocytosis after four weeks of treatment as compared to control group. Biochemically, the results revealed that IM convinced a significant elevation of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities, as well as serum total bilirubin (TB), direct bilirubin (DB) and indirect bilirubin (IB), globulins, urea, creatinine, potassium (K+), pro-inflammatory cytokines (tumor necrosis factor- alpha and interleukin-6) levels at the end of experiment matching with the control group. However, IM administration resulted in a significant diminution in the serum of total proteins (TP), albumin, and sodium (Na+) levels, with a significant increase and decrease respectively in the levels of lipid peroxidation and antioxidant biomarker in the hepatic and renal tissues of rats after four weeks of treatments as compared to control group. Histopathologically, IM administration revealed marked degenerative and necrotic alterations in the liver and kidney. Conversely, LC treatment at two doses (200 and 400 mg) ameliorated IM-induced alterations in the blood picture, oxidative damage and inflammation in the liver and kidneys.Finally, it could be concluded that treatment with LC at two doses (200 and 400 mg) ameliorated IM-induced oxidative damage, alterations in the hematology, liver and kidney function tests, as well as their histopathology. However, administration of LC at a dose of 400 mg/kg BW showed better protective effects against IM-induced hepato-nephrotoxicity as compared to the low dose (200 mg/kg BW).

Methanol extract of Artemisia brevifolia as a curative agent against CCl4 induced nephrotoxicity in albino rats

Carbon tetrachloride (CCl4) is a Potential nephrotoxin that causes severe and prolonged chemical toxicity. Investigations have been accomplished on numerous species of genus Artemisia, but the plant Artemisia brevifolia has hardly been used in this respect. The present study was considered to ascertain the effects of “Artemisia brevifolia plant extract” against CCl4 prompted nephrotoxicity in male albino rats. Forty-eight male albino rats were allocated into eight groups containing 6 rats in each. Group I was the control group. Group II was given dimethyl sulfoxide (DMSO) (1 ml/kg) orally. Group III was treated with dissolved CCl4 in olive oil (1 ml/kg). Group IV was given CCl4 + Silymarine. Group V and VI were administered with Artemisia brevifolia extract (150 and 300 mg/kg respectively) + CCl4. Group VII and VIII were provided with only 150 and 300 mg/kg extract of Artemisia brevifolia respectively. Results displayed that CCl4 administration significantly (p < 0.05) reduced the activity of antioxidant enzymes like catalase (CAT), peroxidase (POD), Superoxide dismutase (SOD), glutathione (GSH), glutathione reductase (GSR), glutathione-S-transferase (GST), albumin, creatinine clearance and Comet parameters (head length, % in head) while increased the level of thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H2O2), urea, creatinine, urobilinogen, urinary proteins and comet parameters (number of comets, tail length, comet length, tail moment, % in tail). The administration of Artemisia brevifolia significantly (p < 0.05) improved the histopathology of renal tissues. The results revealed that Artemisia brevifolia has protective consequences against CCl4 induced kidney damage.

Effect of Trigonella Foenum against Ethylene Diamine Tetra Acetic Acid induced Nephrotoxicity in Male Albino Rats

Background Nephrotoxicity is a complication due to the effect of some toxic chemicals on kidney. Current study planned to screen the effect of Trigonella foenumaqueous seeds extracts on EDTA induced nephrotoxicity. Trigonella foenum known for its various medicinal properties is also a natural antioxidant and a free radical scavenger with no documented evidence as a nephron-protective agent. Objective To investigate the protective effects of aqueous seed extracts of Trigonella foenum. Material and Methods The present study was used 40 male albino rats (Rattus albinus) with weight of (150 ± 10) g with divided into four groups: control gp; EDTA gp (95 mg/kg); Trigonella foenum gp (500 mg/kg) and EDTA + Trigonella f oenum gp by gastric tube daily for 4 weeks. Blood urea, creatinine, GFR, creatinine clearance, MDA and GPx analyses and microscopic examination of kidney were performed. Results In the present study, Blood samples were taken from all groups and concentration of serum urea, creatinine, GFR, Creatinine clearance, MDA and GPx were determined. Histopathological observations were observed in kidney tissue. Data were analyzed using analysis of variance (ANOVA). EDTA induced an increase in urea and creatinine as well as there was a decrease in the concentration of GFR and creatinine clearance. The level of MDA was increase while the concentration of GPx was decrease in the serum of EDTA group. The aqueous extracts of Trigonella seeds significantly prevented renal damage by normalizing increased levels of renal markers. The correction of oxidative stress biomarkers was consistent with amelioration of the histopathological changes induced by EDTA. Hence, it is suggested that ameliorative effect of aqueous extract of Trigonella foenumagainst EDTA induced nephrotoxicity. Conclusion The present data suggest that aqueous extract of Trigonella foenum exhibits reno-protective effect in EDTA induced renal damage.

Modulation of nephrotoxicity induced by gentamicin with bone marrow mesenchymal stem cells and Moringa oleifera extract

The study was undertaken to evaluate the protective effect of bone marrow mesenchymal stem cells (BM-MSCs) and Moringa oleifera extract (MOE) against gentamicin (GN)-induced nephrotoxicity in male albino rats. Thirty two adult male rats were divided into four groups including the control group, the group injected i.p with a single dose of GN (100 mg/kg b.w), the group treated orally with MOE (400 mg/kg b.w) for 6 days then injected with a single dose of GN and the group was injected with a single dose of BM-MSCs (5x105cells) by tail vein then injected with GN. At the end of experiment blood and kidney tissue samples were collected for estimation of different biochemical parameters. The results recorded a significant increase in BUN, serum KIM-1, cystatin C, creatinine, sodium and renal MDA accompanied with a significant decrease in serum calcium, renal GSH, SOD and CAT in GN alone-treated group as compared to control group. Co administration of MOE or BM-MSCs before GN injection improved all above parameters when compared with GN administered group. It could be concluded that MOE and BM-MSCs have a therapeutic and protective action against AKI induced by GN administration which manifested by lowering kidney markers and MDA contents and elevation in antioxidant profile.

Modulatory effect of vitamin C on Gentamicin induced nephrotoxicity in male albino Rats (histological effect)

AbstractBackground: Gentamicin (GM) is an aminoglycoside antibiotic used as bactericidal and effective antibiotic against Gram-negative and limited Gram-positive organisms however nephrotoxicity is one of its side effect.Aim of the work: This study was designed to investigate the effect of vitamin C on the Gentamicin induced histological renal damage.Material and Methods: paraffin sections from rat kidneys were obtained from thirty rats divided in to two groups, control “Group I” and experimental group. The experimental group was divided into groups II and III. Groups II received Gentamicin (70 mg/kg/day I.M) for two weeks, groups III received vitamin C (0.2 mg/kg/day I.P) with Gentamicin for two weeks, Sections stained with Hematoxylin and eosin, PAS, Toluidine blue and Crossman’s stain then examined by light microscopy. Measurements of urea and creatinine in blood for rats in all groups were done followed by statistical analysis of the data. Other specimens were prepared and examined by electron microscopy.Results: L.M of kidney sections showed marked tubular damage especially at PCT in group II. These findings were less manifested by using Vitamin C in group III. These histological changes were confirmed by histochemical stain, image analysis as well as TEM and also proved by measurement of urea and creatinine in blood. The detected morphological, biochemical and functional changes in kidney due to reactive oxygen species that cause nephrotoxicity. Conclusion: The use of vitamin C as antioxidant can improve the renal damage caused by GM.

Codeine-mediated Haematoxicity, Hepatotoxicity and Nephrotoxicity in Male Albino Rats

Objectives: This study aimed to investigate the effects of codeine administration on some haematological and biochemical indices in rats.&#x0D; Materials and Methods: Therapeutic dose (5 mg/kg/day), high dose (25 mg/kg/day) and extreme dose (50 mg/kg/day) of codeine were administered orally to rats for 28 days. Twenty-four hours after the last codeine administration, blood, liver and kidney were removed from the animals after an overnight fast and analysed for their haematological and biochemical parameters.&#x0D; Results: Results obtained revealed that codeine administration significantly reduced the levels of white blood cells (WBC), red blood cell (RBC) and platelet count (PLT) and increased the levels of mean corpuscular haemoglobin (MCH) and mean corpuscular volume (MCV)while it resulted in non-significant changes in other haematological parameters examined when compared with control rats. Codeine intake significantly increased plasma levels of alkaline phosphatase (ALP), aspartate aminotransferase (AST), creatinine and urea while its reduced total protein levels. Hepatic and renal thiobarbituric acid reactive substances (TBARS) levels were significantly increased by codeine administration while levels of endogenous antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) were reduced.&#x0D; Conclusions: This study confirmed the risk of increased oxidative stress, haematoxicity, hepatotoxicity and nephrotoxicity due to codeine administration. Although codeine is reported to be effective in pain management, its toxicity should be kept in mind.

Attenuation of cisplatin-induced nephrotoxicity by ethanol extract of seeds of Lens culinaris medik

Aim: The present study was undertaken to evaluate the potential role of ethanol extract of seeds of Lens culinaris in attenuation of Cisplatin-induced nephrotoxicity in male Albino rats. Materials and Methods: Seeds of Lens culinaris were powdered, defatted and ethanol extract was prepared by hot extraction method. The ethanol extract so prepared was subjected to preliminary phytochemical evaluation and fingerprint analysis using high performance thin layer chromatography. Nephroprotective potential of extract was evaluated at 200 and 400 mg/kg b.w. in both curative and prophylactic regimens in male Albino rats. Nephrotoxicity was induced by single intra peritoneal injection of Cisplatin at a dose of 5 mg/kg b.w. Nephroprotective activity was assessed by determining serum markers, urinary parameters, lipid peroxidation and antioxidant levels in renal tissue. Results: Cisplatin had induced marked acute renal toxicity as manifested by a significant increase in serum marker levels, urinary total protein, lipid peroxidation and decrease in urinary creatinine, catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH). The administration of extract significantly attenuated the Cisplatin-induced nephrotoxicity remarkably by restoring the biochemical and oxidative stress markers in both curative and prophylactic regimens in a dose dependent manner. Histological and immunohistochemical studies also substantiated the biochemical studies. Conclusion: The findings of the present study provides corroborative scientific evidence for the attenuation of Cisplatin-induced nephrotoxicity by seeds of Lens culinaris and validates the ethno-medicinal use of this seeds as renoprotective agent.