Nephrotoxicity In Adult Male Rats Research Articles

Therapeutic and antioxidant effects of lactoperoxidase on aflatoxin B1-induced nephrotoxicity in adult male rats

Background and objective Aflatoxin B1 (AFB1), a type of mycotoxin, is present in food and feed and is toxic to both people and animals. Histological effects of AFB1 on the rat kidney have not been well understood. The objective of this study was to evaluate the therapeutic effect of lactoperoxidase (LPO) against aflatoxin B1-induced nephrotoxicity in a trial to improve its clinical use. Materials and methods Adult male Wistar rats (150–200 g b.w) were randomly divided into four groups (10 rats each): (1) healthy control group, (2) healthy rats treated IP with LPO (50mg/kg/day) for 6 weeks, (3) rats intoxicated orally with AFB1 (80 µg/ kg/day) for 6 weeks, and (4) Animals treated with LPO for 6 weeks after intoxication with AFB1. Results and conclusion The results showed that LPO was successful in reducing aflatoxin B1-induced nephrotoxicity after 6 weeks of treatment. This was demonstrated by the significant decrease in blood urea, urea nitrogen, creatinine, uric acid, potassium, magnesium, phosphorus, TNF-α, IL-1β, as well as kidney NO, MDA, and DNA damages matched with a significant increase in CD4 and albumin levels as well as kidney GSH and SOD. Furthermore, the LPO was successful in aflatoxin B1-induced tissue degenerations, reflecting its therapeutic potential. In conclusion, due to their antioxidant and radical scavenging properties, LPO may be as effective in improving nephrons from aflatoxin B1-induced nephrotoxicity.

LCZ696 (sacubitril/valsartan) protects against cyclophosphamide-induced nephrotoxicity in adult male rats: Up-regulation of Apelin-13/ACE2, miR-200, and down-regulation of TGF-β/SMAD 2/3 and miR-192

BackgroundCyclophosphamide (CP) is a widely used chemotherapeutic drug. However, the associated nephrotoxicity restricts its clinical use. AimThe present research was designed to study the impact of LCZ696 (LCZ); which is a combination of Sacubitril/Valsartan compared to valsartan (VAL) on CP-induced nephrotoxicity. Main methodsSixty adult male Wistar rats were randomly and equally assigned into 6 groups as follows: Control, LCZ (30 mg/kg, p.o.), VAL (15 mg/kg, p.o.), CP (200 mg/kg, single dose, i.p.), CP/LCZ, and CP/VAL groups. LCZ and VAL were given once daily for 6 days prior to CP (groups 5 & 6). At the end of the experiment, kidney functions, oxidants/antioxidants, inflammatory and fibrotic biomarkers in renal tissues were assessed. Further, immunohistochemical, and histomorphometric analyses were carried out. Key findingsIn comparison with CP-treated rats, LCZ resulted in a significant reduction in serum urea (26.6 %) and creatinine (63 %), moreover it decreased renal content of reactive oxygen species (ROS), zinc finger E-box-binding homeobox (ZEB)-1, SMAD2/3, plasminogen activator inhibitor (PAI)-1, fibronectin, histone deacetylase (HDAC)-4, nuclear factor-kappa B (NF-κB) and miR-192 expression by ~40–60 % as well as the immunohistological expressions of transforming growth factor-β (TGF-β) and anti-phospho Histone (H2AX) by ~75 % reduction. Whereas the renal total antioxidant capacity (TAC), apelin-13, miR-200 expression, and the immunoreactivity of angiotensin-converting enzyme 2 (ACE2) were enhanced by ~3–4-folds. Noteworthy, the prophylactic effect of LCZ was superior to VAL on the histomorphometric and immunohistological levels. SignificanceProphylactic administration of LCZ protected against CP-induced nephrotoxicity via up-regulating apelin-13/ACE2, miR-200, and down-regulating TGF-β/SMAD 2/3 and miR-192.

Ameliorative Effect of Eruca sativa Seeds and Its Rutin on Gentamicin‑Induced Nephrotoxicity in Male Rats via Targeting Inflammatory Status, Oxidative Stress and Kidney Injury Molecule-1 (KIM-1)/Cystatin C Expression

BACKGROUND: Nephrotoxicity of Gentamicin (GM), an important aminoglycoside, is still a serious issue in clinical use. Therefore, natural products are currently being used as an alternate source of medicinal substances by researchers all over the world for new medication molecules. Eruca sativa shows several health benefits that appear to be associated with the content of flavonoids. Therefore, the objective of the present study was to evaluate the effect of E. sativa seed extract (ESE) and its active flavenol rutin (RUT) in GM-induced nephrotoxicity in adult male rats. METHODS: The animals were divided into 10 groups: a control group, a groups administered 150 mg/kg body weight (BW) of ESE, a group administered 300 mg/kg BW of ESE, a group administered with 50 mg/kg BW of RUT, a group administered with 100 mg/kg BW of RUT, a GM-nephrotoxic group, and four GM-nephrotoxic groups treated with the same doses of ESE and RUT as previous groups. The treatments were given orally for 4 weeks. Following the treatments animals in all groups were sacrificed. The blood samples were drawn, and the kidney tissue samples were collected for further analysis.RESULTS: ESE alleviated the nephrotoxic effects of GM as it decreased the serum levels of creatinine, urea, Na+, K+, tumor necrosis factor-α (TNF- α), and interleukin-1β (IL-1β). Moreover, ESE was linked with kidney injury molecule-1 (KIM-1) and Cystatin C mRNA downregulation. Although treatment with pure RUT induced the same modulation of ESE in GM- nephrotoxic rats, pure RUT was more effective than ESE in the modulation of oxidative kidney injury.CONCLUSION: The present study revealed the health-promoting effects of ESE or RUT in the attenuation of GM-induced nephrotoxicity.KEYWORDS: nephrotoxicity, gentamicin, Eruca sativa, rutin, inflammation, KIM-1/cystatin C expression

The potential protective role of taurine against 5-fluorouracil-induced nephrotoxicity in adult male rats

Nephrotoxicity is common with the use of the chemotherapeutic agent 5-Fluorouracil (5-FU). The current study aimed to investigate the probable protective effect of taurine (TAU) against 5-FU-induced nephrotoxicity in rats using biochemical, histological and ultrastructural approaches. Twenty-four rats were equally divided into control, TAU, 5-FU and 5-FU+TAU groups.5-FU significantly elevated levels of blood urea nitrogen (BUN), creatinine, and uric acid; while it reduced activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). Also, 5-FU induced significant elevation in malondialdehyde (MDA) levels accompanied with marked decline in γ-glutamyltranspeptidase (GGT) and alkaline phosphatase (AP) levels in kidney tissues. These biochemical alterations were accompanied by histopathological changes marked by destruction of the normal renal structure, in addition to ultrastructural alterations represented by thickened and irregular glomerular basement membranes, congested glomerular capillaries, damaged lining fenestrated endothelium, mesangial cells hyperplasia with expanded mesangial matrix, and distorted podocyte’s processes. Also, the proximal (PCT) and distal (DCT) convoluted tubules showed thickened basement membranes, destructed apical microvilli and loss of basal infoldings of their epithelial cells.Administration of TAU to 5-FU-treated rats reversed most of the biochemical, histological, and ultrastructural alterations. These results indicate that TAU has a protective effect against 5-FU-induced nephrotoxicity.

Aged garlic extract ameliorates the oxidative stress, histomorphological, and ultrastructural changes of cisplatin-induced nephrotoxicity in adult male rats.

Aged garlic extract (AGE) is a natural dietary substance having different antioxidant free-radical-scavenger compounds that ameliorates the toxicity of the oxidative stress. This study aimed to investigate the effect of AGE on cisplatin (CP)-induced nephrotoxicity in rats. Twenty-four, adult male Wistar albino rats were randomly divided into four groups namely control, AGE-treated (a single oral dose of 250 mg/kg/day for 21 days), CP-treated (a single intraperitoneal dose of 7.5 mg/kg on Day 16), and AGE + CP-treated (AGE at a dose of 250 mg/kg/once daily for 21 days and a single dose of CP of 7.5 mg/kg intraperitoneally on Day 16). Body weight and absolute and relative kidney weights of each rat were calculated. Serum creatinine, uric acid, and urea levels were determined. Level of malondialdehyde and reduced glutathione and activity of superoxide dismutase and catalase of renal tissues were measured. Renal specimens from each rat were prepared for both light and electron microscopic examinations. Interstitial cell infiltration, hemorrhage, glomerular atrophy, necrosis, and tubular degeneration were observed after CP treatment. Superoxide dismutase and catalase activities and glutathione level were significantly decreased and malondialdehyde level was significantly increased in CP-treated rats compared with AGE + CP-treated animals. A remarkable improvement in the histopathological and ultrastructural changes induced by CP in renal tissues was observed in AGE + CP-treated rats. AGE exhibited antioxidant effect that could ameliorate the nephrotoxic effects of CP.

Curative Role of D-Penicillamine versus Combined Garlic and Silymarin Extracts on Lead-Induced Nephrotoxicity and Oxidative Stress in Adult Male Albino Rats

Background Lead (Pb) poisoning is still an important global health problem, especially in developing countries. Lead has been extensively used for many years ago, and it will continue to be used in future. Aim of work: This study was conducted to compare the curative role of D-penicillamine versus combined garlic and silymarin extracts for treating nephrotoxicity in adult male rats exposed to Pb for 3 months. Material and methods: The study was conducted on 70 adult male albino rats divided into 7 groups each of 10 rats, where they received all chemicals by oral gavage. Groups I & II were the negative and positive control rats, respectively. Group III received 25 mg/kg/day D-penicillamine for 1 month (4th month). Group IV received combined garlic 20 mg/kg/day+ silymarin 200 mg/kg/day for 1 month (4th month). Group V received 20 mg/kg/day Pb acetate for 3 months. Group VI received Pb acetate for 3 months followed by D-penicillamine for another 1 month, with the previously mentioned doses. Group VII received Pb acetate for 3 months followed by combined garlic & silymarin for another 1 month, with the previously mentioned doses. At the end of the experimental period (4 months), Pb-level in blood, urine & kidney tissue, kidney function tests (blood urea and serum creatinine) and serum malondialdehyde (MDA) & glutathione peroxidase (GSH-Px) were measured. Light microscopic examination of hematoxylin and eosin stained kidney tissue was performed to detect histopathological changes. Results: Lead administration significantly elevated blood lead level (BLL), kidney lead level (KLL), urinary lead level (ULL) and malondialdehyde (MDA), while glutathione peroxidase (GSH-Px) showed significant decrease when compared with the negative control rats. In Pb treated group, histopathological examination of the kidney revealed extensive tubular damage by presence of necrotic epithelial cells, tubular degeneration, necrosis, cell swelling, mononuclear cell infiltration, and degenerated organelles. Kidney functions didn't show any significant differences among all groups. Treatment of rats by D-penicillamine or combined garlic & silymarin extracts resulted in significant decrease in Pb-levels and MDA with a significant increase in blood GSH-PX levels. Also, significant improvement of lead induced histopathological lesions in the kidneys was observed. Combined garlic and silymarin extract treatment showed more significant improvement than D-penicillamine treated Pb-administered groups, in most of the tested parameters. Conclusion: Both D-penicillamine and combined garlic & silymarin extracts can reduce lead induced nephrotoxicity and oxidative stress. Moreover, garlic & silymarin curative effect is better than that of D-penicillamine. Recommendations: Exposure of the population to lead must be controlled. Search for sensitive blood or urinary marker for early detection of kidney damage and further studies are needed to consider a combination of garlic and silymarin is effective in the treatment of lead-induced toxicities.

Effect of pomegranate seed oil against gentamicin -induced nephrotoxicity in rat.

Gentamicin, an important aminoglycoside, is used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. It is a nephrotoxic antibiotic, which causes acute tubular necrosis, and its toxicity remains a major problem in clinical use. This study investigates the effect of pomegranate seed oil (PSO) on gentamicin-induced nephrotoxicity in adult male rats. Animals were randomly divided into four groups. Group one was treated with saline (1ml/kg, i.p.), group 2 received gentamicin 80mg/kg/day for 6days and groups 3 and 4 received PSO 0.32 and 0.64mg/kg/day i.p. respectively, 1h before gentamicin. Serum urea, creatinine levels, urinary glucose and protein concentrations were evaluated as the markers of acute renal failure. Renal antioxidant indicators such as thiobarbituric acid-reactive substance (TBARS), and total thiol contents, were also determined. A significant elevation of serum creatinine and urea levels as well as urine glucose and protein concentrations were observed in gentamicin treated group. Gentamicin also caused a significant decrease in total thiol content and a significant increase in TBARS levels in kidney homogenate samples. PSO pretreatment resulted in a significant and dose-dependent decrease in serum creatinine and urea levels as well as urine glucose and protein concentrations when compared with gentamicin treated alone. PSO also significantly reversed the gentamicin-induced depletion in total thiol content and elevation in TBARS in kidney homogenate samples. The results of the present study indicate that PSO clearly attenuated gentamicin-induced nephrotoxicity, but elucidation of the mechanism(s) of this protection needs more investigation.