Renal Toxicity In Rats Research Articles

Nephroprotective effects of Piper nigrum extracts against monosodium glutamate-induced renal toxicity in rats

BackgroundThe toxicological effects of monosodium glutamate (MSG), widely used as a food additive, are a major public health challenge. This research aimed to investigate the nephroprotective effects of methanol and n-hexane extracts of Piper nigrum (MEPN and HEPN, respectively) against MSG-induced renal toxicity in rats. Materials and methodsThe phytochemicals, vitamins, and in vitro antioxidant activities were determined using standard protocols. Acute toxicity was determined with thirty-two Swiss albino mice, while thirty male Wistar albino rats were used for the nephroprotective study. The rats were randomly distributed into 6 experimental groups (n = 5). Group 1 (baseline) was not induced or treated; groups 2–6 were given 2 g/kg body weight of MSG. Additionally, group 2 received normal saline; groups 3–6 were given 250 and 500 mg/kg body weight of MEPN and HEPN, respectively. MSG was administered alone for 21 days, after which MSG was concomitantly administered with the extracts for additional 28 days. After treatment, biochemical tests were done on the serum, and a histopathological examination was determined with the kidney. ResultsBoth extracts scavenged 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and reduced ferric ions to ferrous ions in the Ferric Reducing Antioxidant Power (FRAP) assay, with MEPN having higher efficacy. The extracts also ameliorated lipid peroxidation and increased the activities of superoxide dismutase and catalase, as well as the level of reduced glutathione. In addition, intervention with MEPN and HEPN provided nephroprotective effects by decreasing urea and creatinine levels and also improved the histo-architecture of the kidney. This efficacy could be due to the rich phytochemicals and antioxidant vitamins previously identified in the plant. ConclusionsThese findings are critical in focusing attention on abolishing the use of MSG in our food sector and highlights the health benefits of incorporating P. nigrum into our food to avert food and drug toxicity.

Effect of some foods on glutathione synthesis to reduce hepatic and renal toxicity in rats

Effect of some foods on glutathione synthesis to reduce hepatic and renal toxicity in rats

Effect of Telmisartan and Quercetin in 5 Fluorouracil-Induced Renal Toxicity in Rats.

The present study was designed to evaluate the possible synergistic effects of telmisartan and quercetin in 5 fluorouracil (5-FU) induced nephrotoxicity in rats. Forty male rats were randomly divided into five groups: The negative control group, the positive control group that received 5-FU, the telmisartan group, receiving 10 mg/kg, the quercetin group, receiving 80 mg/kg, and the combination of telmisartan and quercetin group. All the treatments were given orally for 14 days. A single intraperitoneal injection of 5-FU (150 mg/kg) on day 13 of the experiment was given except for the negative control group. On the 15th day after scarification, approximately 5 mL of blood was collected and used for measurement of CBC, urea, creatinine, and uric acid. The kidneys were used for histopathological examination and for the measurement of kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), Cystatin C (Cys-C), and total antioxidant capacity (TAOC). The combination therapy significantly attenuated the levels of tissue KIM-1, NGAL, Cys-C, and serum uric acid as well as blood inflammatory markers, Neutrophil/Lymphocyte (NLR), Monocyte/Lymphocyte (MLR), and Platelets/Lymphocyte ratios (PLR), and restored the TAOC. The histopathological findings greatly support the biochemical tests. The results strongly suggest the renoprotective effects of telmisartan and quercetin in combination against the nephrotoxic effect of 5-FU through decreasing the levels of KIM-1, NGAL, and cys-C, and the novel inflammatory markers of kidney injury like NLP, MLR, and PLR, as well as decreasing uric acid and restoring the TAOC. The proposed mechanism could be the additive inhibitory effect on RAS provided by both telmisartan and quercetin.

The Possible Protective Effect of Galantamine against Paracetamol Induced Hepatic and Renal Toxicity in Rats

The Possible Protective Effect of Galantamine against Paracetamol Induced Hepatic and Renal Toxicity in Rats

Protective effect of acetylcysteine against thiamethoxam-induced hepatic and renal toxicity in rats

Protective effect of acetylcysteine against thiamethoxam-induced hepatic and renal toxicity in rats

Effects of Co-administration of Pyridoxine in Two Different Doses with Methotrexate-induced Nephrotoxicity in Rats

Nephrotoxicity is defined as rapid deterioration in kidney functions that arises from direct exposure to a drug or its metabolite. Methotrexate is an anti-metabolite used in low doses for autoimmune and inflammatory disorders and high doses for different malignancies. Pyridoxine is the usual form of vitamin B6 included in pharmaceutical products. This study is designed to examine the effect of pyridoxine in two different doses, each co-administered with methotrexate at 20 mg/kg made renal toxicity in rats through the involvement of Nrf2/HO-1 molecular mechanism in this respect. The animals used in this research were allocated to four distinct groups (each group with 10 rats) of both sexes; as control, MTX, pyridoxine 33 mg/kg and MTX, Pyridoxine 100 mg/kg, and MTX. Serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL), and NrF2/HO-1 signaling pathway were determined. Administration of Pyridoxine (33 mg/kg intraperitoneally) in combination with MTX showed no significant differences (p >0.05) as compared to the MTX group. At the same time, administration of pyridoxine (100 mg/kg intraperitoneally) in combination with methotrexate showed a significant reduction in serum activities of both neutrophil gelatinase associated lipocalin (NGAL) and creatinine (p is less than 0.05) and significant upregulation in Nrf2/HO-1 signaling pathway each compared to corresponding levels in MTX-only group. In conclusion, this study demonstrated that when pyridoxine (100 mg/kg IP) was administered in combination with methotrexate, the renal toxicity was reduced as a result.

Effect of Nigella sativa L. Seed on the Kidney of Monosodium Glutamate Challenged Rats.

Monosodium glutamate (MSG) consumption is responsible for a wide spectrum of health hazards including nephrotoxicity. The search for phytochemical strategies having broad safety profile to counter MSG toxicity is worthwhile. Nigella sativa L. seed (NSS) is very promising in this regard owing to its antioxidant and cytoprotective nature. Therefore, we attempted to investigate the potential protective effect of NSS on MSG-induced renal toxicity in rats. To accomplish this objective, fifteen adult Wistar albino rats were randomly and equally divided into three groups for 21 days: the control group received no treatment, MSG group supplemented with MSG at a dose of 30 g/kg feed, and MSG + NSS group supplemented with MSG at the same previous dose in conjugation with NSS at a dose of 30 g/kg feed. MSG and its combination with NSS failed to cause any significant difference in the kidney function parameters in comparison with the control. A significant elevation in lipid peroxides (LPO) level, glutathione-S-transferase activity and total antioxidant capacity (TAC) and a significant reduction in superoxide dismutase activity were found in MSG group. LPO level and TAC in MSG intoxicated rats significantly normalized by NSS ingestion. NO level showed absence of significant difference among all experimental groups. MSG elicited histopathological lesions such as decreased glycoprotein content and fibrosis however, NSS succeeded in enhancing all these features. MSG group showed positive glutathione reductase and superoxide dismutase 2 immuno-expression whereas, MSG + NSS group showed weak immunostaining. A significant increase in the number of apoptotic cells was observed in MSG group compared to the control. On the other hand, MSG + NSS group exhibited a significant decrease in the number of apoptotic cells. NSS mitigated MSG-induced renal impairments by ameliorating oxidative stress and exerting anti-apoptotic effect.

Forskolin alleviates cisplatin-induced acute renal toxicity in rats.

Renal toxicity correlated with cisplatin administration curbs its clinical application. Accordingly, the identification of novel protective agents is important. Forskolin provides anti-inflammatory, anti-oxidant as well as anti-cancer effects. This study aimed to explore the nephroprotective effect of forskolin in a model of cisplatin-induced acute renal toxicity in rats in addition to exploring the possible mechanisms. Rats were sorted into four groups: control group, cisplatin group, cisplatin/forskolin group that was given forskolin (10 mg/kg, i.p.) 1 week before cisplatin and forskolin-only group. Nephrotoxicity markers were tested in the blood. Tissues were used to assess histopathology, oxidative stress, inflammation and apoptosis. In cisplatin-injected rats, the nephrotoxicity indices were particularly increased. Cisplatin markedly reduced the levels of reduced glutathione and superoxide dismutase. Also, malondialdehyde and Nicotinamide adenine dinucleotide phosphate oxidase were increased. In addition, the pro-inflammatory cytokines and caspase-3 were elevated. Moreover, the epidermal growth factor expression was significantly reduced. Furthermore, marked histopathological changes were noted in the tissues of cisplatin-injected rats. Forskolin attenuated nephrotoxicity markers, inflammation, oxidative stress and apoptotic insults provoked via cisplatin. Moreover, cisplatin cytotoxic activity was not modulated by forskolin in human cultured cancerous cell lines. Forskolin provides significant protection from cisplatin-evoked nephrotoxicity enhancing its therapeutic index.

Antitumor and Protective Activity of TVLE against CdCl2-Induced Renal Damage in Rats.

<b>Background and Objective:</b> Cadmium is a heavy metal that has a wide range of applications in human existence. Cadmium may bind to the protein metallothionein and decrease kidney function once it enters the body. The purpose of this study was to investigate the renal protective activity of TVLE against CdCl<sub>2</sub>-induced renal toxicity in rats. <b>Materials and Methods:</b> TVLE was prepared and characterized using instrumental analysis and spectral data. Furthermore, the IC<sub>50</sub> of TVLE against the Vero renal carcinoma cell line was calculated. Adult albino rats were used to assess the renal protective activity of TVLE (150 and 300 mg kg<sup>1</sup> b.wt.) in CdCl<sub>2</sub>-treated rats. <b>Results:</b> IC<sub>50 </sub>of TVLE against Vero cell line equals 148.25 μg mL<sup>1</sup>. The daily oral administration of TVLE at concentrations of 150 and 300 mg kg<sup>1</sup> b.wt. for 21 days to CdCl<sub>2</sub>-treated rates resulted in a significant improvement in tumour volume and tumour weight, urea, creatinine, uric acid, TNF-α, NOx, TBARs, GSH, CAT, SOD, GPx and VEGF-C gene expression in CdCl<sub>2</sub>-treated rats. Furthermore, TVLE almost normalized these effects in renal histoarchitecture. <b>Conclusion:</b> The biochemical, histological and MRI examinations of the current study suggested that TVLE have renal protective activity against CdCl<sub>2</sub>-induced renal toxicity in rats.

Nephrotoxicity of nickel nano and microparticles in rat- a comparative, time dependent study with special reference to antioxidant defence system

A comparative and time dependent study on the effects of nickel oxide nano and nickel oxide microparticles (5 mg/kg body weight) each, has been performed in the kidney of male Wistar rats at two intervals of 15 and 30 days. Morphological, functional changes and effects on antioxidant enzymes in the kidney were studied. Exposure to both, NiONPs and NiOMPs significantly enhanced the generation of reactive oxygen species viz. malondialdehyde, hydrogen peroxide and nitric oxide in rat kidney. However, increase was higher in NiONPs treated rats than NiOMPs treated rats. Diminished values for reduced glutathione and enzymes, that is, superoxide dismutase, glutathione peroxidise and catalase confirmed the role of oxidative stress in NiONPs induced nephrotoxicity. Increased oxidative DNA damage and histopathological changes further supported this hypothesis. Present results suggest that nanoparticles of nickel are more toxic to kidney than nickel metal ions. Reactive oxygen species are a critical factor in NiONPs induced renal toxicity in rat.

Nano-Resveratrol: A Promising Candidate for the Treatment of Renal Toxicity Induced by Doxorubicin in Rats Through Modulation of Beclin-1 and mTOR.

Background: Although doxorubicin (DXR) is one of the most used anticancer drugs, it can cause life-threatening renal damage. There has been no effective treatment for DXR-induced renal damage until now. Aim: This work aims at examining the potential impact of nano-resveratrol (N-Resv), native resveratrol (Resv), and their combination with carvedilol (Card) against DXR-induced renal toxicity in rats and to investigate the mechanisms through which these antioxidants act to ameliorate DXR nephrotoxicity. Method: DXR was administered to rats (2 mg/kg, i.p.) twice weekly over 5 weeks. The antioxidants in question were taken 1 week before the DXR dose for 6 weeks. Results: DXR exhibited an elevation in serum urea, creatinine, renal lipid peroxide levels, endoglin expression, kidney injury molecule-1 (KIM-1), and beclin-1. On the other hand, renal podocin and mTOR expression and GSH levels were declined. In addition, DNA fragmentation was markedly increased in the DXR-administered group. Treatment with either Resv or N-Resv alone or in combination with Card ameliorated the previously measured parameters. Conclusion: N-Resv showed superior effectiveness relative to Resv in most of the measured parameters. Histopathological examination revealed amelioration of renal structural and cellular changes after DXR by Card and N-Resv, thus validating the previous biochemical and molecular results.

Fluvastatin alleviates doxorubicin-induced cardiac and renal toxicity in rats via regulation of oxidative stress, inflammation, and apoptosis associated genes expressions

Doxorubicin (DOXO) is a cytostatic agent used in the chemotherapy protocol of several cancers for more than 40 years, but usage of this drug in cancer treatment has been limited due to severe renal and cardiac tissue toxicities that may result in death in patients. Fluvastatin (FV) is a fully synthetic hydroxymethyl glutaryl coenzyme A (HMG-CoA) reductase inhibitor used as a cholesterol-lowering agent in patients with hypercholesterolemia. Previous studies revealed that FV also exhibits antioxidant, anti-inflammatory, and antitumor activity. Additionally, our previous study indicated that FV exerts a prophylactic effect on DOXO-induced testicular toxicity by preventing lipid peroxidation, supporting the antioxidant system, and regulating the blood-testis barrier-associated genes expression. Herein, we purposed to evaluate the possible therapeutic and the protective effects of FV on the DOXO-induced cardiac and renal toxicitiy model by histochemical, immunohistochemical, biochemical, and real-time polymerase chain reaction (real-time PCR) analyses. Results point out protective use of FV exerts a beneficial effect by repressing lipid peroxidation and by regulating the inducible nitric oxide synthase (iNOS), nitric oxide synthase endothelial (eNOS), nuclear factor kappa-B (NF-κB), and Caspase-3 (Casp3) protein and mRNA expressions, which play an important role in mediating DOXO-induced renal and cardiac toxicity mechanisms. In conclusion, FV may be a candidate agent for the prevention of renal and cardiac toxicities in cancer patients receiving DOXO chemotherapy.

Carbamazepine-induced renal toxicity may be associated with oxidative stress and apoptosis in male rat

Carbamazepine (CBZ) is the antiepileptic drug used in epilepsy and some psychiatric disorders. Besides its widely used, many adverse effects have been reported including hematotoxicity, hepatotoxicity, endocrine disorders, and testicular damages due to oxidative stress. However, the role of CBZ on renal toxicity is not fully known. In this study, we attempted to explain the connected mechanisms by focusing on the metabolism of CBZ-induced renal toxicity in rats. Twenty male Wistar-Albino rats were randomized into 2 groups (n = 10); control (1 mL/day distilled water, orally) and CBZ (25 mg/kg/day CBZ, orally) groups. After 60 days, TAS (total oxidant status) and TOS (total oxidant status) levels, histopathological features, some genes involved in apoptosis, 8-hydroxy-2-deoxyguanosine (8-OHdG) activity, and apoptotic cells were assessed of kidney tissue. The oxidative stress index (OSI) was measured from TAS and TOS levels. TOS levels and OSI significantly increased, while TAS levels decreased in the CBZ group relative to the control group. Histopathological observations, Caspase-3 (Casp3), Poly [ADP-ribose] polymerase-1 (PARP-1), 8-OHdG immunoreactivities, and apoptotic cells markedly raised in the CBZ group compared with the control group. Also, mRNA expression of Cytochrome c (Cytc) and CASP3 significantly increased in the CBZ group compared to the control group. In conclusion, long-term use of CBZ may promote renal damage in rats by inducing oxidative stress and apoptosis.

Zinc Oxide Nanoparticles Ameliorate Dimethylnitrosamine-Induced Renal Toxicity in Rat.

Dimethylnitrosamine (DMN) is an established carcinogen. It is toxic to several organs, viz., the liver, kidney, and lungs, and immune system. Several drugs have been used in the past to modulate its toxicity using experimental animal models. The present study was designed to investigate the effect of zinc oxide nanoparticles (ZnONPs) on renal toxicity caused by DMN in laboratory rat. Since oxidative mechanisms are mainly involved in its toxicity, the proposed study focuses on the amelioration of oxidative stress response by ZnONPs, if any. The present results show that administration of ZnONPs (50mg/kg body weight/rat) to DMN (2μl/100g body weight/rat)-treated rats diminuted the concentration of malonaldehyde, H2O2, and NO in the kidney. However, reduced glutathione (GSH) concentration increased after ZnONP treatment. Results on glutathione S-transferase and glutathione peroxidase favored its antioxidative effects. These results are supported by the recovery of oxidative DNA damage and less pronounced histopathological changes in the kidney. It is hypothesized that ZnONPs might be toxic to renal tissue; however, its strong therapeutic/antioxidative potential helps in ameliorating DMN-induced renal toxicity in rat.

Syzygium cumini (L) Extract Ameliorates Aluminium Chloride-Induced Acute Hepatic and Renal Toxicity in Rats

Syzygium cumini (L) Extract Ameliorates Aluminium Chloride-Induced Acute Hepatic and Renal Toxicity in Rats

Renoprotective and therapeutic effects of newly water, ethanol, and butanol ginseng fractions in hypertensive and chronic kidney disease with L-NAME

The present study investigated the protective and treatment effects of different ginseng fractions against L-NAME–induced renal toxicity in rats. The data obtained demonstrated that L-NAME significantly increased creatinine, urea, KIM-1, and lipocalin-2 levels in serum; and also increased renal MDA and eNOS levels compared with the control group. Three bioactive fractions were newly extracted from ginseng, analyzed by GC-MS analysis, and were examined for antimicrobial, prebiotic, and histological activities. All ginseng fractions improved such histological changes, as reflected by significant reductions in creatinine, urea, KIM-1, and LCN-2 levels in serum, and renal MDA and eNOS contents in tissue homogenate. The water ginseng fraction (WGF) has the highest prebiotic index of 4.7 toward Lactobacillus reuteri, and can improve the renal functions more than butanol ginseng fraction (BGF) and ethanol ginseng fraction (EGF). These three ginseng fractions significantly reversed L-NAME–induced depletion in the TNF-α gene expression level. Interestingly, WGF was able to improve the renal functions more than BGF and EGF. L-NAME led to alterations in the histological structure and functions of renal tissue of rats and ginseng supplementation could offer greater protection against these changes. Moreover, the WGF exhibited superior renoprotection properties when compared with the other two fractions: BGF and EGF, and the reference drug losartan.

Protective effects of vitexin on cadmium-induced renal toxicity in rats.

Cadmium (Cd) is an industrial contaminant that poses severe threats to human and animal health. Vitexin (VIT) is a polyphenolic flavonoid of characteristic pharmacological properties. We explored the curative role of vitexin on Cd-induced mitochondrial-dysfunction in rat renal tissues. Twenty-four rats were equally divided into four groups and designated as control, Cd, Cd + vitexin and vitexin treated groups. The results showed that Cd exposure increased urea and creatinine levels while decreased creatinine clearance. Cd reduced the activities of antioxidant enzymes, i.e., catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione content in the Cd exposed group. Cd exposure significantly (p < 0.05) elevated the reactive oxygen species (ROS) and Thiobarbituric acid reactive substances (TBARS) levels in rat kidney. Cd also caused a significant (p < 0.05) reduction in the mitochondrial TCA-cycle enzymes, including isocitrate dehydrogenase, succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, and malate-dehydrogenase activities. Besides, mitochondrial respiratory chain enzymes, including NADH-dehydrogenase, coenzyme Q-cytochrome reductase, succinic-coenzyme Q, and cytochrome c-oxidase activities were also decreased under Cd exposure. Cd exposure also damaged the mitochondrial membrane potential (MMP). However, VIT treatment potentially reduced the detrimental effects of Cd in the kidney of rats. In conclusion, our study indicated that the VIT could attenuate the Cd-induced renal toxicity in rats.

Quinacrine ameliorated Cisplatin‐induced renal toxicity via modulation of Sirtuin‐1 and its downstream inflammatory and apoptosis pathways

Cisplatin is an effective and widely used chemotherapeutic agent, while underlying renal toxicity is a major limitation for its use. Quinacrine, is an FDA approved antimalarial agent that is known for its anti-inflammatory effect. It has been shown that quinacrine is therapeutically beneficial in cancer, lupus erythematosus and cutaneous sarcoidosis, however, its use to protect against cisplatin toxicity has not been investigated. In this study, we investigated the ameliorative effect of quinacrine against cisplatin induced renal toxicity in rats and the potential molecular mechanism of quinacrine action. Cisplatin toxicity was induced by a single intraperitoneal injection of 10 mg/kg at day 5. Reno protective effect of quinacrine was assessed by intraperitoneal injection of 10 mg/kg/day for the whole-time course of the experiment (10 days). Quinacrine increased rats’ survival rate from 50% (cisplatin group) to 87.5%, with significant decrease in relative kidney weight to body weight, serum creatinine and urea levels in addition to significant reduction in renal tissue fibrosis compared with cisplatin group. Moreover, quinacrine attenuated cisplatin-induced oxidative stress upregulation as indicated by significant decrease in renal malondialdehyde concentration and significant increase in renal total antioxidant capacity compared with cisplatin group. Mechanistically, quinacrine significantly upregulated renal tissue concentration of sirtuin-1 (Sirt-1) which significantly downregulated the inflammatory markers: Intercellular Adhesion Molecule-1 (ICAM-1) and tumor necrosis factor-α (TNF-α). In addition, quinacrine significantly prevented cisplatin-induced apoptosis as evident by decreased renal tissue expression of caspases (1, 3, 8 and 9), decreased the apoptotic proteins BAX and P53 and increased the anti-apoptotic protein BCL2 compared with cisplatin group. Altogether, this study proposes, for the first time, that quinacrine ameliorated cisplatin-induced renal toxicity via upregulation of Sirt-1, downregulation of inflammatory markers (ICAM-1 and TNF-α), restoring oxidative balance and suppressing apoptosis.

Protective effects of resveratrol on kidney function tests and renal histopathology in carbon tetrachloride-induced renal toxicity in rats

Protective effects of resveratrol on kidney function tests and renal histopathology in carbon tetrachloride-induced renal toxicity in rats

Protective effects of resveratrol on kidney function tests and renal histopathology in carbon tetrachloride-induced renal toxicity in rats

In this study, it was aimed to investigate the protective effect of Resveratrol, which has a strong antioxidant effect on kidney tissues of rats experimentally induced with carbon tetrachloride with nephrotoxicity, by kidney function tests and histopathology. For this purpose, 32 male Wistar Albino rats were used. The subjects were randomly selected, 1st group control, 2nd group CCl4, 3rd group Resveratrol. The 4th group was divided into 4 groups as CCl4 + Resveratrol. At the end of the experiment, animals were sacrificed under anesthesia and kidney samples were taken in 10% formalin solution for histopathological analysis. In the histopathological examination, it was found that the rats in the control and Resveratrol groups had normal kidney histological structure. In CCI4 group, severe hydropic degeneration in tubules epithelium, mild coagulation necrosis in tubules epithelium and severe hyperemia in the vessels were observed. When kidney tissues of rats were examined in CCI4 + Resveratrol group, mild hydropic degeneration in tubules epithelium and mild hyperemia in vessels were observed. When the kidney tissues of the rats in the Resveratrol group were examined, it was observed that they had a normal histological appearance. As a result, it was determined that Resveratrol has a protective effect on kidney damage caused by CCI4.