Histopathological Examination Of Kidney Tissues Research Articles

Water-soluble phenolics from Phoenix dactylifera fruits as potential reno-protective agent against cisplatin-induced toxicity: pre- and post-treatment strategies

Nephrotoxicity is the major side effect of cisplatin, an effective platinum-based chemotherapeutic drug that is applicable in the treatment of several solid-tissue cancers. Studies have indicated that certain water-soluble phenolics offer renal protection. Thus, this study investigates the role of pre and post-treatment of rats with water-soluble phenolics from Phoenix dactylifera (PdP) against nephrotoxicity induced by cisplatin. Rats were either orally pretreated or post-treated with 200 mg/kg body weight of PdP before or after exposure to a single therapeutic dose of cisplatin (5 mg/kg body weight) for 7 successive days intraperitoneally. The protective effects of PdP against Cisplatin-induced nephrotoxicity was based on the evaluation of various biochemical and redox biomarkers, together with histopathological examination of kidney tissues. The composition, structural features, and antioxidative influence of PdP were determined based on chromatographic, spectroscopic, and in vitro antioxidative models. Cisplatin single exposure led to a substantial increase in the tested renal function biomarkers (uric acid, creatinine, and urea levels), associated with an increase in malondialdehyde indicating lipid peroxidation and a significant decline (p < 0.05) in reduced glutathione (GSH) levels in the renal tissue when compared with the control group. A marked decline exists in the kidney antioxidant enzymes (catalase, SOD, and GPx). Nevertheless, treatment with PdP significantly suppressed the heightened renal function markers, lipid peroxidation, and oxidative stress. Spectroscopic analysis revealed significant medicinal phenolics, and in vitro tests demonstrated antioxidative properties. Taken together, results from this study indicate that pre- and/or post-treatment strategies of PdP could serve therapeutic purposes in cisplatin-induced renal damage.

Effects of adenosine triphosphate, Lacidipine, and Benidipine on 5-fluorouracil-induced kidney damage in rats.

In the present study, the protective effects of adenosine triphosphate (ATP), Benidipine, and Lacidipine on potential kidney damage induced by 5-fluorouracil (5-FU) were investigated in rats. Totally 48 rats were divided into 8 groups: healthy (HG), 5-FU (FUG), ATP+5-FU (AFU), Benidipine+5-FU (BFU), Lacidipine+5-FU (LFU), ATP+Benidipine+5-FU (ABFU), ATP+Lacidipine+5-FU (ALFU) and Benidipine+Lacidipine+5-FU (BLFU). In a 10-day period, ATP (4 mg/kg) was administered intraperitoneally, and Benidipine (4 mg/kg) and Lacidipine (4 mg/kg) were administered orally once a day. On days 1, 3, and 5, 5-FU (100 mg/kg) was administered intraperitoneally one hour after the drug was administered. Afterward, the rats were euthanized, and kidney tissues were removed. An analysis of malondialdehyde, total glutathione, superoxide dismutase, and catalase was performed on tissues, as well as a histopathological examination. A creatinine and blood urea nitrogen analysis were performed on blood samples. It was revealed that 5-FU decreased the amount of total glutathione, superoxide dismutase, and catalase activities in rat kidney tissues and increased malondialdehyde. Further, increased serum creatinine and blood urea nitrogen levels, as well as histopathological examination of kidney tissues, were found in the 5-FU group. ATP+Benidipine and ATP treatments were the most effective in preventing both biochemical and histopathological changes induced by 5-FU. A treatment with Benidipine improved biochemical and histopathologic data, but not to the same extent as a treatment with ATP+Benidipine and ATP. As a result of Lacidipine+ATP combination, 5-FU-induced biochemical changes in kidney tissue were partially inhibited, but the degree of histopathologic damage remained unchanged. Neither Benidipine+Lacidipine nor Lacidipine showed a protective effect on both biochemical changes and histopathologic damage. It may be possible to prevent nephrotoxicity by adding ATP + Benidipine or ATP to 5-FU treatment.

Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations.

Chronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to investigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes in CKD. Eighty adult male Sprague Dawley rats were randomly assigned to one of six groups, including control, nephropathy, nephropathy + conditioned media (CM), nephropathy + Br-MSCs, nephropathy + Br-MSCs derived exosomes (Br-MSCs-EXOs), and nephropathy + Br-MSCs + Br-MSCs-EXOs. Before administration, Br-MSCs and Br-MSCs-EXOs were isolated, identified, and labeled with PKH-26. SOX2, Nanog, and OCT3/4 expression levels in Br-MSCs and miR-29b, miR-181, and Let-7b in both Br-MSCs and Br-MSCs-EXOs were assayed. Twelve weeks after transplantation, renal function tests, oxidative stress, expression of the long non-coding RNA SNHG-7, autophagy, fibrosis, and expression of profibrotic miR-34a and antifibrotic miR-29b, miR-181, and Let-7b were measured in renal tissues. Immunohistochemical analysis for renal Beclin-1, LC3-II, and P62, Masson trichome staining, and histopathological examination of kidney tissues were also performed. The results showed that Br-MSCs expressed SOX2, Nanog, and OCT3/4, while both Br-MSCs and Br-MSCs-EXOs expressed antifibrotic miR-181, miR-29b, and Let-7b, with higher expression levels in exosomes than in Br-MSCs. Interestingly, the administration of Br-MSCs + EXOs, EXOs, and Br-MSCs improved renal function tests, reduced renal oxidative stress, upregulated the renal expression of SNHG-7, AMPK, ULK-1, Beclin-1, LC3, miR-29b, miR-181, Let-7b, and Smad-7, downregulated the renal expression of miR-34a, AKT, mTOR, P62, TGF-β, Smad-3, and Coli-1, and ameliorated renal pathology. Thus, Br-MSCs and/or their derived exosomes appear to reduce adenine-induced renal damage by secreting antifibrotic microRNAs and potentiate renal autophagy by modulating SNHG-7 expression.

Sıçanlarda Doksorubisin Kaynaklı Böbrek Hasarı Üzerine Selenyum ve N-(p-Amilsinnamoil) Antranilik Asit’in Etkisi

Doxorubicin (DOXR) is one of the essential antitumor drugs. However, its serious adverse effects in many organs limit the clinical use of DOXR. This study aimed to investigate the effect of selenium (Se) and N-(p-Amilcinnamoyl) anthranilic acid (ACA) on kidney tissue in DOXR-administered rats. The rats in the study were divided into six groups (n=10); Control, DMSO, DOXR, DOXR+Se, DOXR+ACA and DOXR+Se+ACA. At the end of the study, intracardiac blood was drawn from rats, and kidney tissues were removed. Urea and creatine levels were measured in serum samples of rats. In addition, histopathological examination of kidney tissue was determined by H&amp;amp;E staining, and 8-OHdG expression was determined by immunohistochemical analysis. Urea and creatine levels increased with DOXR decreased in serum samples after Se and ACA treatments (p&amp;lt; 0.05). While glomerular atrophy, tubular and glomerular dilatation, vascular occlusion and degeneration of tubular epithelial cells were observed in the DOXR group, significant improvement was observed in the Se and ACA treatment groups. In addition, Se and ACA treatments reduced DOXR-induced 8-OHdG expression (p&amp;lt; 0.05). These findings indicated that Se and ACA could be used as critical therapeutic agents to suppress renal dysfunction and oxidative DNA damage that can occur after DOXR-induced kidney injury.

Lactoferrin alleviates cyclophosphamide induced-nephropathy through suppressing the orchestration between Wnt4/β-catenin and ERK1/2/NF-κB signaling and modulating klotho and Nrf2/HO-1 pathway

AimsCyclophosphamide is an alkylating agent with vast arrays of therapeutic activity. Currently, its medical use is limited due to its numerous adverse events, including nephrotoxicity. This study aimed to follow the molecular mechanisms behind the potential renoprotective action of lactoferrin (LF) against cyclophosphamide (CP)-induced renal injury. Materials and methodsFor fulfillment of our aim, Spragw-Dwaly rats were orally administrated LF (300 mg/kg) for seven consecutive days, followed by a single intraperitoneal injection of CP (150 mg/kg). Key findingsTreatment of CP-injured rats with LF significantly reduced the elevated creatinine and blood urea nitrogen (BUN), markedly upregulated Nrf2/HO-1 signaling with consequent increase in renal total antioxidant capacity (TAC) and decrease in renal malondialdehyde (MDA) level. Furthermore, LF treatment significantly reduced the elevated renal p-ERK1/2 expression, tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), nuclear factor-kappa B (NF-κB) levels in CP-treated animals. Interestingly, LF treatment downregulated Wnt4/β-catenin signaling and increased both renal klotho gene expression and serum klotho level. Furthermore, LF treatment reduced apoptosis in kidney tissue via suppressing GSK-3β expression and modulating caspase-3 and Bcl2 levels. Histopathological examination of kidney tissue confirmed the protective effect of LF against CP-induced renal injury. SignificanceThe present findings document the renoprotective effect of LF against CP-induced nephropathy, which may be mediated via suppressing ERK1/2/ NF-κB and Wnt4/β-catenin trajectories and enhancing klotho expression and Nrf2/HO-1 signaling.

Corni Fructus Alleviates UUO-Induced Renal Fibrosis via TGF-β/Smad Signaling.

Renal fibrosis is a type of chronic kidney disease (CKD) induced by infiltration of inflammatory cells, myofibroblast accumulation, and ECM production in the kidney. From a long time ago, Corni Fructus (CF) is known to supplement the liver and kidney with its tepid properties. In this study, we investigated the renal protective mechanism of CF, which is known to supplement the kidney, in rat model of unilateral ureteral obstruction (UUO). After inducing UUO through surgery, the group was separated (n = 8) and the drug was administered for 2 weeks; normal rats (normal), water-treated UUO rats (control), CF 100 mg/kg-treated UUO rats (CF100), and CF 200 mg/kg-treated UUO rats (CF200). As a result of histopathological examination of kidney tissue with H&E, MT, and PAS staining, it was confirmed that the infiltration of inflammatory cells and the erosion of collagen were relatively decreased in the kidneys treated with CF. Also, CF significantly reduced the levels of MDA and BUN in serum. As a result of confirming the expression of the factors through western blotting, CF treatment significantly reduced the expression of NADPH oxidase and significantly regulated the AMPK/LKB1/NF-κB pathway associated with inflammation. In addition, it downregulated the expression of major fibrotic signaling factors, such as α-SMA, collagen I, MMP-2, and TIMP-1, and significantly regulated the TGF-β1/Smad pathway, which is known as a major regulator of renal fibrosis. Taken together, these findings indicate that CF can alleviate renal fibrosis by regulating the TGF-β1/Smad pathway through inhibition of oxidative stress in UUO.

Naringenin alleviates hyperglycemia-induced renal toxicity by regulating activating transcription factor 4-C/EBP homologous protein mediated apoptosis.

Endoplasmic reticulum (ER) dysfunction plays a prominent role in the pathophysiology of diabetic nephropathy (DN). This study aimed to investigate the novel role of Naringenin (a flavanone mainly found in citrus fruits) in modulating ER stress in hyperglycemic NRK 52E cells and STZ/nicotinamide induced diabetes in Wistar rats. The results demonstrated that Naringenin supplementation downregulated the expression of ER stress marker proteins, including p-PERK, p-eIF2α, XBP1s, ATF4 and CHOP during hyperglycemic renal toxicity in vitro and in vivo. Naringenin abrogated hyperglycemia-induced ultrastructural changes in ER, evidencing its anti-ER stress effects. Interestingly, treatment of Naringenin prevented nuclear translocation of ATF4 and CHOP in hyperglycemic renal cells and diabetic kidneys. Naringenin prevented apoptosis in hyperglycemic renal cells and diabetic kidney tissues by downregulating expression of apoptotic marker proteins. Further, photomicrographs of TEM confirmed anti-apoptotic potential of Naringenin as it prevented membrane blebbing and formation of apoptotic bodies in hyperglycemic renal cells. Naringenin improved glucose tolerance, restored serum insulin level and reduced serum glucose level in diabetic rats evidencing its anti-hyperglycemic effects. Histopathological examination of kidney tissues also confirmed prevention of damage after 28days of Naringenin treatment in diabetic rats. Additionally, Naringenin diminished oxidative stress and improved antioxidant defense response during hyperglycemic renal toxicity. Taken together, our study revealed a novel role of Naringenin in ameliorating ER stress during hyperglycemic renal toxicity along with prevention of apoptosis, cellular and tissue damage. The findings suggest that prevention of ER stress can be exploited as a novel approach for the management of hyperglycemic nephrotoxicity.

Ameliorative effect of apelin-13 against renal complications in L-NAME-induced preeclampsia in rats.

Pre-eclampsia (PE) accompanying acute liver and kidney injury has remained a master cause of both fetal and maternal mortality and morbidity. Vasoactive mediators, oxidative stress and inflammatory imbalanceshave an important role in PE pathogenesis. Apelin is an adipokine that improves endothelial dysfunction; has anti-inflammatory and antioxidant effects; moreover, its level reduced during PE. This study aimed to explore the effects of apelin-13 administration on preeclampsia-associated renal dysfunction and proteinuria. Thirty-three pregnant female rats were divided into three groups; group: 1 (normal pregnant rats), group: 2 (preeclamptic rats); where rats were injected subcutaneously with 75 mg L-NAME/ kg body weight/day beginning from 9th to 20th day of pregnancy andgroup 3 (apelin-13 treated preeclamptic rats); In which L-NAME-induced preeclamptic rats were subcutaneously injected with 6 × 10−8 mol apelin-13/kg body weight/twice daily starting from 6th to 20th day of pregnancy. In all groups, mean arterial blood pressure, total urine protein, serum urea, creatinine, nitric oxide (NO), endothelin-1 (ET-1), interleukin–6 (IL-6) and malondialdhyde (MDA) were measured. Histopathological examination of kidney tissues was also done. preeclamptic rats showed significantly increased mean arterial blood pressure, total urine proteins, serum urea, creatinine, ET-1, IL-6, and MDA, but revealed a significantly decreased serum NO level. On the other hand, apelin treatment significantly improved these parameters together with amelioration of kidney histoarchitecture in the treated group. In conclusion, apelin may be a potentially curative candidate for prohibiting kidney damage and have a therapeutic benefit in PE rat models.

Black mulberry fruit extract alleviates streptozotocin-induced diabetic nephropathy in rats: targeting TNF-α inflammatory pathway.

This study was designed to investigate the effect of Morus nigra fruit extract in retarding the progression of diabetic nephropathy in streptozotocin (STZ)-induced diabetic rats. Diabetic male Wistar rats were injected with black mulberry fruit extract (BMFE) at doses of 150 and 300mg/kg body weight. After 4weeks, microalbuminuria was estimated in addition to serum concentrations of glucose, insulin, creatinine and albumin. The study revealed a significant amelioration of all the measured parameters in diabetic animals. In addition, MDA, lipid peroxide levels and catalase activity were also improved. The histopathological examination of kidney tissues revealed significant improvement of the pathological changes and glomerular sclerosis in diabetic rats treated with BMFE. Treated rats showed downregulation of TNF-α, vascular cell adhesion molecule-1 (VCAM-1) and fibronectin mRNA expression. The ameliorative effect of BMFE on diabetic nephropathy is not only through its potent antioxidant and hypoglycaemic effects but also through its downregulation of TNF-α, VCAM-1 and fibronectin mRNA expression in renal tissues of diabetic-treated rats. Therefore, BMFE as dietary supplement could be a promising agent in improving diabetic nephropathy.

Renal protective effects of grape seed extract treatment against Eltroxin-induced hyperthyroidism, kidney damage, and oxidative stress in male mice.

The present study aimed to investigate the influence of grape seed extract (GSE) in renal toxicity, oxidative stress, and Bcl-2 expressions in Eltroxin-induced hyperthyroidism to male mice. GSE was evaluated through oral administration to male mice at dose 50mg/kg daily for 3 consecutive weeks. Eltroxin (100μg/kg) was administered to mice for 3weeks, and the mice were posttreated with GSE for another 3weeks. Results revealed that GSE administered to normal mice did not produce any signs of toxicity and did not cause any biochemical or histopathological changes. Posttreatment of Eltroxin-induced hyperthyroidism mice with GSE daily for 3weeks improved all examined biochemical or histopathological features. Oral GSE can significantly normalize the elevated level of T3 and T4 in hyperthyroidism animals and elevated the reduced levels of TSH. Moreover, serum urea, creatinine, and electrolyte levels were significantly improved. GSE showed a potent antioxidant capacity in all oxidative stress markers assays (TBARS, reduced GSH, GST, SOD, and CAT) of kidney tissue homogenates. Furthermore, histopathological examination of kidney tissue of Eltroxin + GSE-treated group confirms the potential nephroprotective effect of GSE through increasing the anti-apoptotic marker Bcl-2.

Periodontitis aggravates kidney damage in obese mice by MMP2 regulation.

To investigate the effect of periodontitis on the development of kidney damage in obese mice and its possible mechanism. C57 BL/6J mice were fed high‑fat (HF) or low‑fat (LF) diet and then divided into four groups: obesity with periodontitis (HFP), obesity without periodontitis (HFC), normal mice with periodontitis (LFP) and normal mice without periodontitis (LFC). Serum indicators of renal function, namely serum total protein (TP), albumin (ALB), creatinine (Cr) and blood urea nitrogen (UREA) were measured. The histopathological examination of kidney tissues was performed. The expressions of transforming growth factor-β1 (TGF-β1), matrix metalloproteinase-2 (MMP2) and tissue inhibitors of metalloproteinases-1 (TIMP1) were detected by immunohistochemistry and real time RT-PCR. Obesity decreased TP and ALB, and increased serum Cr and UREA levels in normal and periodontitis mice groups, as well as induced glomerular and tubulointerstitial pathologic changes. Tubulointerstitial fibrosis was more severe in HFP group. In obese mice, periodontitis caused the downregulation of MMP2, and upregulation of TIMP1 and TGF-β1 at transcriptional and translational levels. In obese mice, periodontitis may aggravate pathological changes in the kidney. The possible mechanism might lie in downregulation of MMP2 and upregulation of MMP inhibitor, TIMP1, and TGF-β1 (Tab. 1, Fig. 4, Ref. 16).

Nephrotoxicity Induced by Cisplatin Intake in Experimental Rats and Therapeutic Approach of Using Mesenchymal Stem Cells and Spironolactone.

Chronic kidney disease may lead to subsequent tissue fibrosis. However, many factors can combat injurious stimuli in these tissues aiming to repair, heal, and alleviate any disturbance. Chemokines release, migration of inflammatory cells to the affected site, and activation of fibroblasts for the production of extracellular matrix are commonly observed in this disease. In the last years, many studies have focused on spironolactone (SPL), a mineralocorticoid receptor antagonist, and its pharmacological effects. In the present study, SPL was selected as an anti-inflammatory agent to combat nephrotoxicity and renal fibrosis induced by cisplatin. Mesenchymal stem cells (MSCs) were also selected in addition as a referring agent. Renal fibrosis induced by cisplatin intake significantly increased creatinine, urea, nuclear factor kappa B, insulin-like growth factor-1, fibroblast growth factor-23, and kidney malondialdehyde (MDA) content. Hepatocyte growth factor and renal content of reduced glutathione demonstrated a significant decrease. Histopathological examination of kidney tissues demonstrated marked cellular changes which are correlated with the biochemical results. Oral SPL intake (20mg/kg/body weight) daily for 4weeks and MSCs administration (3×106 cell/rat) intravenous to the experimental rats resulted in a significant improvement of both the biomarkers studied and the histopathological profile of the renal tissue. Individual administration of spironolactone and MSCs exhibited a marked anti-inflammatory potential and alleviated to a great extent the nephrotoxicity and renal fibrotic pattern induced by cisplatin.

Effects of benfotiamine and coenzyme Q10 on kidney damage induced gentamicin.

Gentamicin (GM) is an effective antibiotic against severe infection but has limitations related to nephrotoxicity. In this study, we investigated whether benfotiamine (BFT) and coenzyme Q10 (CoQ10), could ameliorate the nephrotoxic effect of GM in rats. Rats were divided into five groups. Group 1 and 2 served as control and sham respectively, Group 3 as GM group, Group 4 as GM+CoQ10 and Group 5 as GM+BFT for 8days. At the end of the study, all rats were euthanized by cervical decapitation and then blood samples and kidneys were collected for further analysis. Serum urea, creatinine, cytokine TNF-a, oxidant and antioxidant parameters, as well as histopathological examination of kidney tissues were assessed. Gentamicin administration caused a severe nephrotoxicity which was evidenced by an elevated serum creatinine, urea and KIM-1 level as compared with the controls. Moreover, a significant increase in serum malondialdehyde, reduced glutathione. Histopathological examination of renal tissue in gentamisin administered group, there were extremly pronounced necrotic tubules in the renal cortex and hyalen cast accumulation in the medullar tubuli. BFT given to GM rats reduced these nephrotoxicity parameters. Serum creatinine, urea, and KIM-1 were almost normalized in the GM+BFT group. Benfotiamin treatment was significantly decreased necrotic tubuli and hyalen deposition in gentamisin plus benfotiamin group. CoQ10 given to GM rats did not cause any statistically significant alterations in these nephrotoxicity parameters when compared with GM group but histopathological examination of renal tissue in GM+CoQ10 administered group, CoQ10 treatment was decreased necrotic tubuli rate and hyalen accumulation in tubuli. The results from our study indicate that BFT supplement attenuates gentamicin-induced renal injury via the amelioration of oxidative stress and inflammation of renal tubular cells.

Protective effect of rutin supplementation against cisplatin-induced Nephrotoxicity in rats

BackgroundCisplatin (CP) is commonly used in the treatment of different types of cancer but nephrotoxicity has been a major limiting factor. Therefore, the present study aimed to study the possible protective effect of rutin against nephrotoxicity induced by cisplatin in rats.MethodsForty male Wistar albino rats were randomly divided into 4 groups. Rats of group 1 control group intraperitoneal (i.p.) received 2.5 ml/kg, group 2 CP group received single dose 5 mg/kg cisplatin i.p. group 3 rutin group orally received 30 mg/kg rutin group 4 (CP plus rutin) received CP and rutin as in group 2 and 3. Kidneys were harvested for histopathology and for the study the gene expression of c-Jun N-terminal kinases (JNK), Mitogen-activated protein kinase 4 (MKK4), MKK7, P38 mitogen-activated protein kinases (P38), tumor necrosis factors alpha (TNF-α), TNF Receptor-Associated Factor 2 (TRAF2), and interleukin-1 alpha (IL-1-α).ResultsThe cisplatin single dose administration to rats induced nephrotoxicity associated with a significant increase in blood urea nitrogen (BUN) and serum creatinine and significantly increase Malondialdehyde (MDA) in kidney tissues by 230 ± 5.5 nmol/g compared to control group. The animal treated with cisplatin showed a significant increase in the expression levels of the IL-1α (260%), TRFA2 (491%), P38 (410%), MKK4 (263%), MKK7 (412%), JNK (680%) and TNF-α (300%) genes compared to control group. Additionally, histopathological examination showed that cisplatin-induced interstitial congestion, focal mononuclear cell inflammatory, cell infiltrate, acute tubular injury with reactive atypia and apoptotic cells. Rutin administration attenuated cisplatin-induced alteration in gene expression and structural and functional changes in the kidney. Additionally, histopathological examination of kidney tissues confirmed gene expression data.ConclusionThe present study suggested that the anti-oxidant and anti-inflammatory effect of rutin may prevent CP-induced nephrotoxicity via decreasing the oxidative stress, inhibiting the interconnected ROS/JNK/TNF/P38 MAPK signaling pathways, and repairing the histopathological changes against cisplatin administration.

Protective Effect of Withania coagulans Fruit Extract on Cisplatin-induced Nephrotoxicity in Rats.

Background:Fruits of Withania coagulans (Solanaceae) reported to possess several bioactive compounds as curative agents for various clinical conditions. Cisplatin is a chemotherapeutic drug to treat sarcomas, carcinomas, lymphomas, cervical cancer, germ cell tumors, etc. The major factor that limits its clinical use is its dose-dependent nephrotoxicity.Aim:To explore the nephroprotective effect of W. coagulans extract and its modulatory effects against cisplatin-induced nephrotoxicity and genotoxicity.Materials and Methods:W. coagulans fruit extract was quantitatively standardized with withaferin A using high-performance thin-layer chromatography. The subacute toxicity study was performed according to OECD guidelines in experimental rats. Nephrotoxicity in rats was induced by a single dose of cisplatin (6 mg/kg, intraperitoneal). Nephroprotective role of W. coagulans fruit extract at different doses had been evaluated. It includes quantification of serum kidney toxicity markers, renal tissue oxidative stress biomarkers and pro-inflammatory cytokines level, DNA fragmentation assay, and histopathological examination of renal tissue.Results:Withaferin A was found 3.56 mg/g of W. coagulans fruit extract. It significantly prevented the rise in serum urea and creatinine level and also preserve rat kidneys from oxidative stress and free radical induced DNA damage. Histopathological study showed extract treatment eliminates tubular swelling, cellular necrosis, and protein cast deposition in cisplatin treated kidney tissue. It averted the decline in glutathione content, activities of superoxide dismutase and catalase. These parameters were restored to near normal levels by extract in a dose of 400 mg/kg, per oral. Conclusion: It can be justified that W. coagulans possess dose dependent protective effect against cisplatin induced kidney damages, primarily through its free radical scavenging and anti inflammatory activitySUMMARY Authentication and standardization of Withania coagulans fruitsSubacute oral toxicity studyEvaluation of nephroprotective activity against cisplatin-induced nephrotoxicityDNA fragmentation assay and histopathological examination of kidney tissue in experimental rats. Abbreviations Used: WHO: World Health Organization, SOD: Superoxide dismutase, CAT: Catalase, HPTLC: High-performance thin layer chromatography, p.o.: Per.oral, i.p.: Intraperitoneal, TNF-α: Tumor necrosis factor-alpha, IL-1β: Interleukin 1-beta, IL-6: Interleukin-6

10-DHGD ameliorates cisplatin-induced nephrotoxicity in rats.

10-DHGD exhibited a marked anti-inflammatory potential, alleviated to a great extent of nephrotoxicity and renal fibrosis induced by cisplatin.

Experimental studies on the Renal Protective effect of Gokshura (Tribulus terrestrisLinn) and Varuna (Crataeva nurvalaBuch-Ham)

Kidney is one of the most vital organs in the body. It is a very sophisticated structure and very complex physiology hence suffers from a variety of specific types of diseases and is also liable to be affected in a number of other systemic conditions of external origin. Moreover, there is no satisfactory treatment for most of the diseases of the kidney, while on the other hand the hospital statistics indicated a rising incidence of kidney diseases in different parts of the world. Standard medical treatment, dialysis and transplant are very expensive propositions and out of reach of the majority hence non-dialytic/non-transplant and economical conservative management is often sought by majority of the patients. In this paper renal protective study has been carried out on aqueous extract of Gokshura (Tribulus terrestris Linn) and Varuna (Crataeva nurvala Buch-Ham) as described in Ayurvedic literature based on their action on urinary system as pre and post treatment in different doses in experimentally induced nephrotoxic animal model with Gentamicin. Parameters like Blood urea and Serum Creatinine estimation, Urine RE/ME and histopathological examination of kidney tissues have been considered for comparative study. The result has been statistically analyzed for its significance. It is observed that Aqueous Extract of Gokshura Fruit and Aqueous Extract of Varun Bark pre treated to induction of nephrotoxicity shown protection to kidney against Gentamicin induced nephrotoxicity in rats considering the above parameters. The role of these 2 drugs may be considered as renal protective effect against drug induced nephropathy.

Polysaccharide extract of Cordyceps sobolifera attenuates renal injury in endotoxemic rats

Extracts derived from Cordyceps have been demonstrated to possess various pharmacological effects, including immunomodulatory, antitumor, hypoglycemic, and antioxidant activities. This study was aimed to clarify the role of CS-P, a polysaccharide fraction isolated from Cordyceps sobolifera, in modulating nephrofunctional damage in a rat model of endotoxemia. CS-P (500mg/kg body weight) was orally administered to rats for 4weeks before the peritoneal injection of lipopolysaccharide (LPS, 10mg/kg body weight). Pre-treatment with CS-P significantly attenuated the deleterious renal functions caused by LPS, i.e., elevated blood urea nitrogen and creatinine as well as urine protein. Histopathological examination of kidney tissues also demonstrated that CS-P improved LPS-induced pathological abnormalities. The induction of inducible nitric oxide synthase and the overproduction of nitric acid by LPS were also significantly reduced by CS-P via inhibiting nuclear factor-κB activation. In addition, CS-P pre-treatment suppressed the plasma levels of tumor necrosis factor-alpha and interleukin-6. Concurrently, CS-P supplementation potently suppressed the LPS-induced rise of lipid peroxidation and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney. The present results suggested that CS-P pre-treatment could protect against LPS-triggered inflammatory responses and renal injury in rats.

Nephrotoxicity of cefepime: A new cephalosporin antibiotic in rats

Objectives:To investigate the nephrotoxic effect and biochemical alterations induced by cefepime in rats.Materials and Methods:Cefepime was administered intramuscularly at doses of 45, 90 and 180 mg/kg b.wt. once daily for 5 consecutive days. The serum and urine samples were used for quantitative determination of urea, creatinine, glucose, total protein, calcium, sodium and potassium. The histopathological examination of kidney tissues was performed 1, 4 and 8 days after the last dose of cefepime administration.Results:Cefepime induced a significant increase in the total amount of urine per day, urea and creatinine concentration in the serum and urine and significant decrease in their clearance. Cefepime also caused a significant gluocosuria and proteinuria and significant decrease in their serum concentrations. The effect of cefepime on serum and urine concentrations of calcium, sodium and potassium were also determined. Cefepime injection in the three tested doses caused renal tubular, glomerular and vascular changes. The severity of these changes was dose dependent. In conclusion, these results suggest a possible contribution of cefepime in the nephrotoxicity and biochemical alterations, especially at high doses. Therefore, the renal functions should be monitored during the cefepime therapy.

Effect of atorvastatin and erythropoietin on renal fibrosis induced by partial unilateral ureteral obstruction in rats

ObjectiveThis work aims at investigating the effects of atorvastatin and erythropoietin (EPO) on tubulointerstitial fibrosis induced by partial unilateral ureteral obstruction (PUUO) in rats.BackgroundRenal fibrosis is the final manifestation of chronic kidney disease. It is one of the biggest problems in nephrology, indicating that patients inevitably reach end-stage renal disease. Atorvastatin has anti-inflammatory, antiproliferative, and immunomodulatory potential. EPO has been demonstrated to play an important cytoprotective role.MethodsFifty adult albino rats were divided into five equal groups: group 1 received saline intraperitoneally and methylcellulose orally for 14 days and served as the negative control; group 2 (sham-operated group) rats underwent the same surgical procedures as group 3 without ureteral obstruction; group 3 rats underwent PUUO without any medication; group 4 rats underwent PUUO and received atorvastatin at a dose of 50 mg/kg orally; group 5 rats underwent PUUO and received EPO at a dose of 3.000 IU/kg daily intraperitoneally. After 14 days, systolic blood pressure was measured. Blood and urine samples were also collected for measurement of serum transforming growth factor-β1, tumor necrosis factor-͍, urea and creatinine, and urinary protein and albumin levels. Renal tissue samples were collected for determination of malondialdehyde and ͍-smooth muscle actin levels, as well as for histopathological and immuonohistochemical examination.ResultsOur results showed that systolic blood pressure; serum levels of transforming growth factor-β1, tumor necrosis factor-α, and malondialdehyde; and biochemical parameters were significantly elevated. Histopathological examination of kidney tissue revealed marked degenerative changes and increased expression of α-smooth muscle actin in group 3 compared with groups 1 and 2. In contrast, biochemical, histological, and immuonohistochemical features in groups 4 and 5 showed significant improvement compared with group 3.ConclusionIt is concluded that both atorvastatin and EPO have renoprotective effects against renal fibrosis, shown by improvement in kidney functions and using fibrosis markers.