Nephrotoxicity In Male Wistar Rats Research Articles

Methyl jasmonate and diphenyl diselenide attenuate diethylnitrosamine and carbon tetrachloride-induced nephrotoxicity in rats via modulation of inflammation and oxidative stress processes

The pathogenesis of toxicity-mediated renal injury has been linked to reactive oxygen species. Therefore, intervention with antioxidant agents as part of therapeutic strategies is necessary. This study investigated the modulatory effects of Diphenyldiselenide (PhSe)2 and Methyl Jasmonate (MJ) against Diethylnitrosamine (DEN) and Carbon tetrachloride (CCL4)-induced nephrotoxicity in male Wistar rats. Forty-eight (48) rats were assigned into six groups of eight animals each. Group 1 served as control, Group 2 received DEN (100mg/kg) + CCL4 (0.5mg/kg), Group 3 received [DEN+CCL4] and treated with MJ (50 mg/kg), Groups 4 and 5 received [DEN+CCL4] and treated with (PhSe)2 (5 mg/kg and 10 mg/kg), and Group 6 received [DEN+CCL4] and treated with quercetin (50mg/kg). Administration of DEN and CCL4 increased serum urea, creatinine and kidney injury molecule-1 (KIM-1) by 97%, 62% and 73%. Furthermore, activities of glutathione-S-transferase, superoxide dismutase and catalase significantly (P<0.05) decreased in [DEN+CCL4] rats. The BCL-2 associated X, caspases -3 and -9 increased in rats administered-[DEN+CCL4]. In addition, TNF-α increased by 117%, myeloperoxidase and nitric oxide level increased by 385% and 65%, respectively in [DEN+CCL4]-administered rats. Histology showed mild vascular congestion and infiltration of inflammatory cells in interstitial spaces in [DEN+CCL4] rats. Interestingly, treatment with methyl jasmonate and diphenyl diselenide attenuated kidney function markers, reduced tissue inflammation and apoptosis status of [DEN+CCL4]-rats. Methyl jasmonate and diphenyldiselenide abate nephrotoxicity caused by combined administration of DEN- and CCL4- via induction of antioxidative and anti-inflammatory activities.

PROTECTIVE EFFECTS OF VITAMIN C ON ACETAMINOPHEN-INDUCED LIVER AND KIDNEY TOXICITY IN MALE RATS

Acetaminophen (paracetamol) is a widely used over-the-counter analgesic and antipyretic medication known for its efficacy and safety when administered within recommended doses. However, overdose or prolonged use of acetaminophen can lead to severe hepatotoxicity and nephrotoxicity, posing a significant public health concern. This study aims to investigate the protective effects of vitamin C on acetaminophen-induced hepatotoxicity and nephrotoxicity in male Wistar rats. Six rats were randomly assigned to seven groups, with Group 1 designated as the control. Groups 2, 4, and 6 were given daily single oral doses of 100, 200, and 400 mg/kg of acetaminophen, respectively. Meanwhile, Groups 3, 5, and 7 received daily single oral doses of 100, 200, and 400 mg/kg of acetaminophen, followed by intraperitoneal administration of 100 mg/kg of vitamin C daily, for 14 days. Liver function markers (AST, ALT, total bilirubin, and total protein) and renal function indicators (urea and creatinine levels) were assessed, alongside antioxidant status in liver and kidney tissues through antioxidant assays (SOD, CAT, GSH, and MDA). The results demonstrated the protective influence of vitamin C on liver and kidney tissues, as indicated by the modulation of biochemical markers. These findings suggest that vitamin C may play a pivotal role in alleviating acetaminophen-induced liver and kidney damage across different dosage regimens, potentially serving as a therapeutic intervention for preventing or treating drug-induced organ injuries. Further investigations are essential to elucidate the underlying mechanisms and validate the translational potential of vitamin C as a protective agent against acetaminophen toxicity.

Renoprotective effects of Cucumeropsis mannii seed oil on cisplatin-induced nephrotoxicity in Wistar rats

BackgroundThe growing prevalence of cancer and the concomitant rise in chemotherapy use have led to an increased incidence of kidney-related diseases, including nephrotoxicity. Cisplatin (CP) is a widely used and potent anticancer drug, but nephrotoxicity limits its clinical application. PurposeOur study aimed to determine the phytochemicals and median lethal dose of Cucumeropsis mannii seed oil (CMSO) using standard methods and to further investigate the effects of CMSO on CP-induced nephrotoxicity in male Wistar rats. MethodsTwenty-one rats (100 to 150 g) were randomly divided into seven groups (n = 3) and treated with CMSO or normal saline for ten days. Group A received 1.0 mL of normal saline, irrespective of the body weight (b.w.). Groups B-D received 2500, 5000, and 7500 mg/kg b.w., respectively, of the CMSO and a single intraperitoneal dose of CP (8 mg/kg) on the seventh day. Groups E and F were administered 2500 mg/kg and 7500 mg/kg b.w., respectively, of the CMSO without CP administration. Group G received a single intraperitoneal dose (8 mg/kg b.w.) of CP on the seventh day without CMSO treatment. ResultsThe analysis of CMSO revealed the presence of various phytochemicals such as hydrogen cyanide, glycosides, saponins, steroids, tannins, alkaloids, terpenoids, phenols, and flavonoids. Acute toxicity testing demonstrated the safety of CMSO up to 5000 mg/kg b.w. We discovered that the CP administration increased serum creatinine (sCr), urea, blood urea nitrogen (BUN), and malondialdehyde (MDA) levels in rats and markedly decreased renal superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities and glutathione (GSH) levels. CMSO attenuated kidney dysfunction, oxidative stress, and lipid peroxidation. Interestingly, CMSO prominently decreased sCr, urea, and BUN levels, boosted the activity of SOD, CAT, and GPx, increased GSH levels, and significantly (p < 0.05) decreased MDA levels. Histological assessment corroborated these biochemical findings. ConclusionOur findings highlight the potential of CMSO as a protective agent against CP-induced nephrotoxicity. The observed effects are attributable to the rich phenolic and flavonoid content of CMSO. These findings have significant implications for developing complementary therapies to mitigate chemotherapy-associated kidney damage, potentially enhancing the safety and efficacy of cisplatin-based cancer treatments. Further investigation is needed to explore the clinical applications of CMSO for cancer patients.

Ezetimibe ameliorates cisplatin-induced nephrotoxicity: A novel therapeutic approach via modulating AMPK/Nrf2/TXNIP signaling.

Cisplatin (Cis) is among the most powerful antineoplastic medications, nevertheless, its serious side effects; particularly nephrotoxicity designates a major concern. Previous studies reported that ezetimibe (Eze), a well-known antihyperlipidemic drug, exerts additional trivial pharmacological effects. In this work, we displayed Eze as an intriguing protective candidate in a cisplatin-induced nephrotoxicity rat model through AMPK activation. Eze (10 mg/kg, p.o.) was administered for two weeks and Cis (10 mg/kg, i.p.) was administered on the 10th day to induce nephrotoxicity in male Wistar rats. Treatment with Eze greatly augmented the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK) and the antioxidant regulator; nuclear factor erythroid 2-related factor 2 (Nrf2), thus, mitigating oxidative injury through induction of the antioxidant enzymes, such as heme oxygenase-1 (HO-1) and glutathione reductase (GR). As well, Eze relieved inflammation by reducing protein expression of thioredoxin-interacting protein (TXNIP) and nucleotide-binding domain-like receptor protein 3 (NLRP3), which led to a decrease in the release of caspase-1, in addition to, the inflammatory markers IL-18and IL-1 β. Besides, Eze ameliorated apoptosis in the renal cells through inhibiting the phosphorylated Apoptosis signal-regulating kinase-1(p-ASK1), caspase-3 and reducing Bax/Bcl2ratio. Correspondingly, histopathological examination corroborated the previous biochemical findings. Collectively, Eze exerts significant renal protection against Cis-induced nephrotoxicity via antioxidant, anti-inflammatory and anti-apoptotic pathways that are probably mediated, at least partly, via activating AMPK/Nrf2/HO-1 pathway and conquering both TXNIP/NLRP3 inflammasome and TXNIP/ASK1 signaling pathways. To confirm the protective effect of Eze via AMPK-activation, an AMPK-inhibitor, dorsomorphin (Dors), when co-administered with Eze abolished its protective effect.

α-Tocopherol Ameliorates Redox Equilibrium Disorders and Reduces Inflammatory Response Caused by Diclofenac-Induced Nephrotoxicity in Male Wistar Rats.

Background Diclofenac (DCF), a nonsteroidal anti-inflammatory drug (NSAID), is widely used for its analgesic and anti-inflammatory properties, but it can also be nephrotoxic. Vitamin E (α-tocopherol) has been shown to protect against renal toxicity caused by various agents, including NSAIDs. This study aims to evaluate the pathophysiology of renal damage and the nephroprotective effect of vitamin E against DCF-induced renal damage in male Wistar rats. Animal and methods Twenty-four male Wistar rats, divided into six equal groups, were used for the study. Group 1 (control group) was treated with distilled water only, while the other groups received either high or low doses of DCF with or without a fixed dose of vitamin E. Renal function was assessed by measuring serum urea, creatinine, and kidney injury molecule-1 (KIM-1). Oxidative damage and renal antioxidant levels were also assessed. Additionally, the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), renal cytokine tumor necrosis factor-α (TNF-α), and histopathological changes were evaluated. Results DCF caused a significant increase in serum urea, creatinine, KIM-1, TNF-α, NF-κB, and malondialdehyde levels compared to the control group. However, in the groups treated with DCF plus vitamin E, a significant reduction (P<0.05) in the levels of pro-inflammatory cytokines and malondialdehyde was observed, along with improvement in renal function indices, superoxide dismutase, catalase, and glutathione peroxidase levels comparable to the control group. The observed renal histopathological changes were consistent with the results of the biochemical parameters between the treated groups and the normal control rats. Conclusion Findings from this investigation suggested that DCF can be nephrotoxic at a certain dose when used for a prolonged duration. Co-administration of vitamin E suppressed the elevated inflammatory cytokines and led to changes in the cell redox-sensitive signaling pathways induced by DCF, with eventual amelioration of the nephrotoxicity.

Isoliquiritigenin pretreatment regulates ER stress and attenuates cisplatin-induced nephrotoxicity in male Wistar rats.

Cisplatin (CP) is a chemotherapeutic drug used to treat solid tumors. However, studies have revealed its nephrotoxic effect. Oxidative stress, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction are involved in CP-induced renal damage. Thus, preconditioning (hormetic effect) of ER stress is a strategy to prevent CP-induced renal damage. On the other hand, isoliquiritigenin (IsoLQ) is recognized as a flavonoid with antioxidant properties and an inducer of ER stress. Therefore, we evaluated the ER stress-inducing capacity of IsoLQ and its possible protective effect against CP-induced nephrotoxicity in adult male Wistar rats. The findings reflected that IsoLQ pretreatment might decrease renal damage by reducing plasma creatinine and blood urea nitrogen levels in animals with CP-induced nephrotoxicity. These may be associated with IsoLQ activating ER stress and unfolded protein response (UPR). We found increased messenger RNA levels of the ER stress marker glucose-related protein 78 kDa (GRP78). In addition, we also found that pretreatment with IsoLQ reduced the levels of CCAAT/enhancer-binding protein-homologous protein (CHOP) and X-box-binding protein 1 (XBP1) in the renal cortex, reflecting that IsoLQ can regulate the UPR and activation of the apoptotic pathway. Moreover, this preconditioning with IsoLQ of ER stress had oxidative stress-regulatory effects, as it restored the activity of glutathione peroxidase and glutathione reductase enzymes. Finally, IsoLQ modifies the protein expression of mitofusin 2 (Mfn-2) and voltage-dependent anion channel (VDAC). In conclusion, these data suggest that IsoLQ pretreatment has a nephroprotective effect; it could functionally regulate the ER and mitochondria and reduce CP-induced renal damage by attenuating hormesis-mediated ER stress.

The Ameliorative Effect of Honey on Lead (Pb) – Induced Nephrotoxicity in Male Wistar Rats

The Ameliorative Effect of Honey on Lead (Pb) – Induced Nephrotoxicity in Male Wistar Rats

Antioxidant activities of reissantia indica willd. (mopane paddle-pod) and nephroprotective effect on paracetamol-induced nephrotoxicity in male wistar rats

Antioxidant activities of reissantia indica willd. (mopane paddle-pod) and nephroprotective effect on paracetamol-induced nephrotoxicity in male wistar rats

Pretreatment of ellagic acid protects ifosfamide-induced acute nephrotoxicity in rat kidneys: A mitochondrial, histopathological and oxidative stress approaches

Ifosfamide (IFO) kidney damage is an important organ toxicity in children and adults undergoing chemotherapy. Previous evidence has shown that IFO toxic metabolites such as acrolein and are associated with mitochondrial dysfunction, depletion of antioxidants, oxidative stress and may predispose the kidney to IFO toxicity. Bioactive food compounds such as ellagic acid (EA) found in fruits has been described as antioxidant and mitochondrial protective agents against toxicity-related mitochondrial damage and oxidative stress. In current study, the protective effects of EA on IFO-induced nephrotoxicity in male Wistar rats were investigated with histopathological, biochemical, and mitochondrial methods. The rats were randomly divided into four groups, control, IFO, IFO + EA, and EA groups. EA (25mg/kg, i.p. daily) were administered to animals for 2 consecutive days and IFO (500mg/kg, i.p.) was administered on third day. The results showed that pretreatment EA significantly increased mitochondrial succinate dehydrogenases (SDH) activity, and protected mitochondrial swelling, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, lipid peroxidation (LPO) and depletion glutathione (GSH). Histopathological findings demonstrated that EA had protective effects and reduced histopathological abnormalities caused by IFO. These results showed that EA administration protects the kidneys against mitochondrial dysfunction, oxidative stress and histopathological abnormality induced by IFO. Taken together, our results demonstrated that EA played a protective role against IFO-induced nephrotoxicity through mitochondrial protection and antioxidant properties.

Protective effect of Geophila obvallata (Shumach) Didr leaf extract and its fractions against cadmium-induced nephrotoxicity in male Wistar rats

Cadmium (Cd) is a known nephro-toxicant. This research determined the ameliorative effects of Geophila obvallata crude methanol extract (Me70) and its fractions on Cd-induced nephrotoxicity in Wistar rats. Male rats were randomly allocated to nine (9) groups of six (6) rats each. Group I was given normal water and feed only. Group II received 0.3 mg Cd/L only for two weeks. Groups III, IV, V, VI and VII were pre-exposed to aqueous, ethyl acetate, hexane, butanol and chloroform fractions of Me70, each at a dose of 50 mg/kg bwt for fourteen (14) days prior to treatment with 0.3 mg Cd/L for a further two weeks. Group VIII was pre-exposed to Me70 at a dose of 50 mg/kg bwt for fourteen (14) days, prior to administration of 0.3 mg Cd/L for fourteen (14) days, while group IX received 50 mg/kg.bwt of Me70 only for fourteen (14) days. The treatments were administered daily for twenty-eight (28) days via oral gavage. Cadmium levels in the kidney tissues of Cd-treated rats increased significantly while their body weights decreased relative to control. The levels of kidney function markers in the plasma, lipid peroxidation levels, catalase activity, metallothionine (MT-1) and kidney injury molecule-1 (KIM-1) mRNA were increased significantly, while glutathione (GSH) levels, activities of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione-s-transferase (GST), and levels of nuclear factor erythroid-2-related factor 2 (Nrf-2), peroxisome proliferator-activated receptor –gamma coactivator- 1-alpha (PGC-1α), heme oxygenase-1 (HO-1) and NADH quinone oxidoreductase-1 (NQ-O1) were decreased significantly in rats treated with Cd-only. Overall, pre-treatment with Me70 produced better protection from the toxic effects of cadmium induction in experimental rats.

The potential protective role of apigenin against oxidative damage induced by nickel oxide nanoparticles in liver and kidney of male Wistar rat, Rattus norvegicus.

Nickel oxide nanoparticles (NiONPs) are involved in several applications but still have some adverse effects. Apigenin (APG) is a widespread natural product with antioxidative, anticancer, and anti-inflammatory properties. The present work aimed to study the protective role of APG against the NiONP-induced toxicity in male Wistar rats. Rats were randomly distributed to one control group and three treated groups. The treated groups were orally administered NiONPs (100mg/kg) alone, APG (25mg/kg) alone, or APG 1h before NiONPs, once daily for 28days. Blood, liver, and kidney were collected after 7, 14, and 28days of administration for Ni accumulation, hematological, biochemical, histological, and transmission electron microscopy (TEM) investigations. As compared to the controls, the administration of NiONPs alone significantly elevated the levels of Ni, malondialdehyde, total cholesterol, low-density lipoprotein cholesterol, creatinine, urea, blood urea nitrogen, and the activity of alanine and aspartate aminotransferases as well as the count of white blood cells. Besides, marked reductions in the activity of superoxide dismutase, and the levels of glutathione, high-density lipoprotein cholesterol, total proteins, albumin, globulin, hemoglobin, packed cell volume, and red blood cell count were reported. Histologically, the liver and kidney of rats administered NiONPs alone showed remarkable disturbances. According to TEM, subcellular alterations were observed in the liver and kidney of rats administered NiONPs alone. In contrast, APG administering before NiONPs substantially alleviated all the studied parameters. In conclusion, APG can ameliorate the NiONP-induced hepatotoxicity and nephrotoxicity in male Wistar rats.

&lt;i&gt;Geophila Obvallata&lt;/i&gt; (Shumach) Didr Protects Against Cadmium-Induced Nephrotoxicity in Male Wistar Rats Via Down-Regulation of KIM-1 and Up-Regulation of Nrf2 Signaling

&lt;i&gt;Geophila Obvallata&lt;/i&gt; (Shumach) Didr Protects Against Cadmium-Induced Nephrotoxicity in Male Wistar Rats Via Down-Regulation of KIM-1 and Up-Regulation of Nrf2 Signaling

NEPHROPROTECTIVE EFFECT OF TUKHME KARAFS (APIUM GRAVEOLENS L.) AGAINST GENTAMICIN INDUCED NEPHROTOXICITY IN EXPERIMENTAL ANIMALS

Tukhme Karafs is the seed of Apium graveolens L., which is an important aromatic plant grown globally as a fresh herb and widely used as salad crop. This seed possesses potential pharmacological activity like hepatoprotective, diuretic and lithotriptic. The present study was designed to evaluate nephroprotective effect of Tukhme Karafs against gentamicin (80 mg/kg BW) induced nephrotoxicity in male Wistar rats. The effect was tested at two dose levels i.e. 500 mg/kg and 1000 mg/kg BW (calculated based on clinical dose mentioned in Unani literature). The study was divided into curative and protective models. The efficacy was determined based on estimation of biochemical parameters (creatinine, uric acid, BUN and serum electrolytes) along with quantification of kidney injury molecule-1 (KIM-1) using ELISA method in kidney tissue homogenate and histopathological study of kidney tissue. The findings of the study showed that Tukhme Karafs at both tested doses showed prominent reduction of biochemical parameters as compared to negative control group in both models. KIM-1 reduction was observed but was not statistically significant in both the models. Histopathological changes showed that drugs have inhibited gentamicin induced injury in both models. These results confirm the nephroprotective effect of Tukhme Karafs.

Standardized aqueous stem bark extract of Gmelina arborea roxb. possesses nephroprotection against adriamycin-induced nephrotoxicity in Wistar rats

Nephrotoxicity is a major limitation of adriamycin (ADR) chemotherapy. We hypothesized that administration of standardized aqueous bark extract of Gmelina arborea Roxb. (GA) (Family; Verbenaceae), a traditional therapeutic agent, may reduce the nephrotoxicity caused by ADR in Wistar rats. The dose-dependent nephroprotective activity of the standardized GA extract was investigated in ADR-induced (20 mg/kg, ip) nephrotoxicity in male Wistar rats (n = 6/group). The lyophilized powder of the aqueous refluxed (4 h) GA extract was administered at 100, 300 and 500 mg/kg doses orally for three consecutive days. Fosinopril sodium (0.09 mg/kg) was used as the positive control. Assessment of biochemical parameters on serum, urine and histopathology on H and E stained kidney sections were done at the end of the intervention. The treatment with GA and fosinopril decreased the elevation of serum creatinine, blood urea nitrogen, cystatin C, β2-microglobulin and loss of total protein in urine in nephrotoxic rats in a dose-dependent manner (p < 0.05). In contrast, serum concentrations of albumin and total protein were increased significantly (p < 0.05). H and E stained kidney sections showed an attenuation of renal parenchymal injury following the treatment. The aqueous extract of GA demonstrated antioxidant potential in vitro. Present findings conclude that the standardized aqueous extract of GA stem bark exerted a dose-dependent protection against ADR-induced nephrotoxicity in vivo and may be a promising adjunct in ADR chemotherapy.

Protective effects of sesamol against cisplatin-induced nephrotoxicity in rats: A mechanistic approach

BackgroundAcute renal failure specifically denotes tubular necrosis due to induced by ischemic injury or drugs, resulting in electrolyte imbalance along with changes in hormonal levels in renal system, causing accumulation of nitrogenous waste in the kidneys. ObjectiveTo explore the role and mechanism of sesamol as renoprotective using cisplatin mediated nephrotoxicity in male Wistar rats. MethodIn male wistar rats, a single dose of 5 mg per kg of body weight, i.p cisplatin was used to induce nephrotoxicity. Renoprotective effect of sesamol was evaluated by analyzing blood, urine, oxidative stress markers and tissue histology. ResultPresent study shows that cisplatin confirms the nephrotoxicity by modifying the urinary, blood and inflammatory parameters in contrast to the vehicle control group. Sesamol at dose levels of 50 and 100 mg/kg body weight, p.o. significantly & dose dependently reverses the changes. Nephroprotective effect of sesamol was abolished by PPAR-γ inhibitor, BADGE (30 mg/kg, i.p.) in rats. ConclusionOur study clearly indicates the nephroprotective activity of sesamol by PPAR-γ agonism against cisplatin-induced nephrotoxicity in rats.

The Preventive Effects of Cynara scolymus Leaf and Flower Extracts on Diethylnitrosamine/ Acetylaminoflourene Induced Nephrotoxicity in Male Wistar Rats

The Preventive Effects of Cynara scolymus Leaf and Flower Extracts on Diethylnitrosamine/ Acetylaminoflourene Induced Nephrotoxicity in Male Wistar Rats

Hepato &amp; nephro protective effects of naringenin-loaded tpgs polymeric nanosuspension against cisplatin-induced toxicity

Cisplatin (Cis-Diammineplatinum (II) dichloride/CIS) is one of the most potent chemotherapeutic agents widely used in treatment of various cancers. Naringenin (NAR), a natural flavonoid, protect against CIS-induced injury in rats without hampering CIS beneficial cytotoxic activity. Even though NAR exhibits therapeutic potency, clinical evolution of the molecule is embarrassed because of very less aqueous solubility which corresponds to low availability at the site of the tumor. In our former analysis, nanosuspension of naringenin (NARNS) was developed by the method of high-pressure homogenization. The study had been continued to evaluate the protective role of D-α-Tocopheryl polyethylene glycol succinate (TPGS) coated NARNS, against oxidative stress-induced hepato and nephrotoxicity in male Wistar rats upon CIS treatment. Induction of acute hepato and neprotoxicity was done by intraperitoneal injection (i.p) injection of CIS (7 mg/kg of body weight) and administration of NAR and NARNS. Administration of NARNS virtually suppressed CIS-induced and liver injury evidenced by a reduction of lipid peroxidation level, blood urea nitrogen, serum uric acid, creatinine and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in rats liver tissue. Histological studies substantiated the biochemical parameters. The study suggests that NARNS has strong hepato and nephroprotective effect compared to NAR.

Time – Course of Sodium Arsenate Induced Hepatotoxicity and Nephrotoxicity in Male Wistar Rats

Arsenic exposure has been implicated by several epidemiological studies as an important metalloid that is currently poisoning millions of people globally. In order to investigate the time – course of arsenic exposure on hepatic and renal toxicity, male albino rats (n=45) were exposed to arsenic (100 ppm, 150 ppm and 200 ppm) for 4, 8 and 12 weeks as sodium arsenate in their drinking water. Control animals (n=15) received distilled water for the same period after which blood and vital organs were removed from the animals and analyzed for alanine amino transaminase (ALT), aspartate amino transaminase (AST) gamma amino transaminase (γGT), alkaline phosphatase (ALP), creatinine and urea spectrophotometrically. Histological changes in hepatocytes was also examined. Before the commencement of arsenic exposure, five animals were sacrificed to obtain baseline data. Significant elevation in plasma ALT, AST, γGT and alkaline phosphatase activities characterized the effect of the arsenical at all doses and time interval relative to the controls. Plasma levels of creatinine and urea were also elevated at all-time intervals in the arsenic group. In most of the cases observed, the elevated level of these biochemical marker in circulation are time – and dose – dose dependent. Hepatic histopathology reveals degeneration of cytoplasmic contents, evidence of necrosis, collapse of central vein, cytoplasmic inclusion and enlarged hepatic sinusoids in arsenic – exposed groups. These findings suggest that different dose regimens of sodium arsenate at different time interval caused degenerative changes in hepatic and renal tissues in rats in dose – and time – dependent fashion. Keywords: Arsenic, Time – course, Hepatotoxicity, Nephrotoxicity DOI: 10.7176/JNSR/9-4-09

The ethanol leaf extract of Andrographis paniculata blunts acute renal failure in cisplatin-induced injury in rats through inhibition of Kim-1 and upregulation of Nrf2 pathway.

Background Cisplatin (CP) is a novel drug of choice in the treatment of cancer but its major limitation is nephrotoxicity, which is dose limiting. Andrographis paniculata (AP) is a common Indian dietary component. It is well known for its medicinal properties. This present study investigated the nephroprotective effect of ethanol leaf extract of Andrographis paniculata (EEAP) on CP-induced nephrotoxicity. Methods CP was used to induce nephrotoxicity in male Wistar rats to study the effect of EEAP on renal damages using hematological parameters, biochemical parameters, histology, and immunohistochemistry studies. Results The effects of EEAP were determined by CP-induced changes in different kidney tissue on antioxidant enzymes, markers of oxidative stress, serum creatinine, and urine parameters. Administration of EEAP (200 mL/kg and 400 mg/kg orally), prior to and following a single dose CP treatment (10 mg/kg i.p), significantly mitigated the CP-induced decrease in antioxidant enzymes, and increase in markers of oxidative stress, serum creatinine, and urinary protein. On histopathological examination of the kidney tissue, there was severe glomerular degeneration and infiltration of inflammatory cells in CP only treated rats, mild glomerular degeneration, and infiltration of inflammatory cells in EEAP pre-treated rats. Furthermore, EEAP activated Nrf2 and mitigated Kim-1 pathways in CP-induced nephrotoxicity. Conclusions The results showed the protective effect of EEAP against CP-induced nephrotoxicity.

Nutritional content of selected species of tropical eggplant fruit (Solanum spp) diet Attenuates hepatic inflammation in high-fat fed male Wistar rats induced with streptozotocin.

Tropical Solanum species contains a high level of phenolic acids and flavonoids, which were found to inhibit some key enzymes associated with the incidence of type 2 diabetes in in vitro and in vivo models based on earlier studies. This study was further designed to compare the nutritional properties, glycemic index, and hypolipidemic and the antioxidant effects of three species of tropical eggplant fruit (Solanum kumba, Solanum aethiopicum, and Solanum gilo) diet on streptozotocin (STZ)‐induced nephrotoxicity in male Wistar rats. The animal model was subjected to high‐fat diet prior to interperitional administration of streptozotocin (35 mg/kg wt); thereafter, the rats were given supplemented eggplant fruit diet, which lasted for 14 days. Determination of lipid content [triglycerides (TG), low‐density lipoproteins (LDLs), high‐density lipoproteins (HDLs), and total cholesterol (TC)], was assessed, while the liver biomarker enzymes alanine aminotransferase (ALT) alkaline phosphatase (ALP) and aspartate aminotransferase (AST), also endogenous enzymes such as superoxide dismutase (SOD) and catalase (CAT), were determined. Histopathological assessment of inflammation was carried out on kidney while the blood urea nitrogen (BUN), uric acid, and creatinine level on the kidney function were determined. The results showed that the groups with supplemented eggplant diet had significant (p < 0.05) reduction in lipid profile, decreased leakages of the liver, and kidney function enzymes while there was restoration of depleted endogenous antioxidant enzymes. The inflammatory cells and fat deposit from the histopathological view were reduced. However, S. kumba had the best nutritional output.