Renal Injury In Rats Research Articles

Protective Role of Quercetin on Thioacetamide-Induced Renal Injury in Adult Male Albino Rats

Background: Thioacetamide (TAA) is a recognized industrial poisonous agent drastically used in animal studies for induction of hepatic necrosis, fibrosis and cirrhosis. It is additionally reported to be nephrotoxic through induction of oxidative stress. Quercetin (QE) has a high antioxidant capacity via free radical scavenging, transition metal ion binding, and lipid peroxidation inhibition. Aim of the work: The goal of this research was to see if QE may help reduce the negative effects of thioacetamide on renal tissue by histological examination of the kidney. Material and methods: Twenty four adult male Albino rats 7–9 weeks old around 180–200g body weight were allocated into 3 groups; Group I (n=8) receiving distilled water, Group II (n=8); rats receiving TAA and Group III (n=8); receiving TAA and QE. Results: Renal tissues were examined under a light microscope stained by Harris Hematoxylin & Eosin (H&E stain), Periodiceeacid Schiff (PAS) andjMasson’srTrichrome for TAA-treated groups revealed severe histopathological changes, whereas specimens obtained from QE-treated groups showed onlywmild changes. Immunohistochemical results corroborated these findings. Conclusion: This study demonstrated the ameliorative consequences of QE in opposition to TAA-induced renal injury in rats. The result of this study might contribute in the development of a novel complementary alternative medication in combating and therapeutic intervention of TAA-induced renal injury. KEY WORDS: Thioacetamide, renal, quercetin, albino rat and histopathology.

The effect of carvacrol on tramadol-induced oxidative renal injury in rats: biochemical and histopathological evaluation

Long-term treatment with tramadol is reported to be toxic to the kidneys. Research shows that tramadol reduces antioxidants and increases oxidants produced in renal tissue. This study aims to investigate the carvacrol effect on tramadol-induced renal injury in rats. The animals were divided into four groups: healthy (HG), individual tramadol (TR), individual carvacrol (CR), and tramadol + carvacrol (TC). Malondialdehyde (MDA), total glutathione (tGSH), glutathione peroxidase (GPO), superoxide dismutase (SOD), total oxidant status (TOS), total antioxidant status (TAS), blood urea nitrogen (BUN), and creatinine (Cr) were measured. Renal tissue was examined histopathologically. MDA, TOS, BUN, and Cr were significantly elevated in group TR and identified as low in group TC compared to group TR but higher than in the HG group. The tGSH, SOD, GPO, and TAS levels were low in group TR and higher in group TC than in group TR but lower than in the HG group. Histological examination of the TR group revealed diffuse necrosis and focal polymorphonuclear leukocytes (PMNLs) in the tubules. In the TC group, tubular atrophy and necrosis were minimal, and PMNL was rare. We observed that tramadol increases oxidants, decreases antioxidants, increases BUN and Cr, and examined whether the toxic effect on renal tissue regressed with carvacrol.

Ethanolic Extracts of Grape and Guava Seeds Ameliorate Gentamicin Induced Acute Renal Injury in Rats

Ethanolic Extracts of Grape and Guava Seeds Ameliorate Gentamicin Induced Acute Renal Injury in Rats

Oxymatrine Alleviates Gentamicin-Induced Renal Injury in Rats.

Gentamicin is an aminoglycoside antibiotic commonly used to treat Gram-negative bacterial infections that possesses considerable nephrotoxicity. Oxymatrine is a phytochemical with the ability to counter gentamicin toxicity. We investigated the effects and protective mechanism of oxymatrine in rats. The experimental groups were as follows: Control, Oxymatrine only group (100 mg/kg/d), Gentamicin only group (100 mg/kg/d), Gentamicin (100 mg/kg/d) plus Oxymatrine (100 mg/kg/d) group (n = 10). All rats were treated for seven continuous days. The results indicated that oxymatrine alleviated gentamicin-induced kidney injury, and decreased rats’ kidney indices and NAG (N-acetyl-beta-d-glucosaminidase), BUN (blood urea nitrogen) and CRE (creatine) serum levels. The oxymatrine-treated group sustained less histological damage. Oxymatrine also relived gentamicin-induced oxidative and nitrative stress, indicated by the increased SOD (superoxidase dismutase), GSH (glutathione) and CAT (catalase) activities and decreased MDA (malondialdehyde), iNOS (inducible nitric oxide synthase) and NO (nitric oxide) levels. Caspase-9 and -3 activities were also decreased in the oxymatrine-treated group. Oxymatrine exhibited a potent anti-inflammatory effect on gentamicin-induced kidney injury, down-regulated the Bcl-2ax and NF-κB mRNAs, and upregulated Bcl-2, HO-1 and Nrf2 mRNAs in the kidney tissue. Our investigation revealed the renal protective effect of oxymatrine in gentamicin-induced kidney injury for the first time. The effect was achieved through activation of the Nrf2/HO-1 pathways. The study underlines the potential clinical application of oxymatrine as a renal protectant agent for gentamicin therapy.

Curcumin alleviates aristolochic acid nephropathy based on SIRT1/Nrf2/HO-1 signaling pathway

Aristolochic acid I (AA-I), presenting in a variety of natural medicinal plants, which could cause tubular epithelial cell injury. Curcumin (CUR), a polyphenolic substance isolated from turmeric, is a natural antioxidant. The aim of this experiment was to investigate whether CUR attenuated AA-I-induced renal injury in rats through the SIRT1/Nrf2/HO-1 signaling pathway. SD rats were treated with AA-I (10 mg/kg) or/and CUR (200 mg/kg) for 28 days to assess the protective effect of CUR on AA-I-induced renal injury in vivo. NRK-52E cells were treated with AA-I (40 μ M) or/and CUR (20 μ M) for 24 h in vitro. The intervention pathway of CUR against oxidative stress injury induced by AA-I was assessed by observing pathological changes, oxidative stress status, apoptosis and the expression of SIRT1/Nrf2/HO-1 signaling pathway-related factors. The results showed that AA-I exposure increased the contents of BUN, Cr, KIM-1, NGAL, ALT and AST in serum. It increased the content of MDA, decreased the activities of SOD, GST, GSH and the content of ATP in renal tissue. Pathological changes such as inflammatory cell infiltration and mitochondrial injury occurred in renal tissue. AA-I exposure resulted in a substantial rise in the levels of BAX, Ccaspase-9, Cleaved Caspase-9, Caspase-3, Cleaved Caspase-3 and a significant decrease in mRNA and protein expression levels of Bcl-2, SIRT1, Nrf2, NQO1, HO-1 and Keap1. However, these changes were reversed by CUR intervention. In summary, AA-I exposure caused mitochondrial dysfunction and triggered apoptosis through the oxidative stress pathway. However, CUR could reduce AA-I-induced renal injury by activating the SIRT1/Nrf2/HO-1 signaling pathway.

Nephro-protective effect of Daphnetin in hyperoxaluria-induced rat renal injury via alterations of the gut microbiota.

It is well proved that hyperoxaluria induces the renal injury and finally causes the end stage kidney disease. Daphnetin (coumarin derivative) already confirmed renal protective effect in renal model, but hyperoxaluria protective effect still unexplore. The objective of this research was to scrutinize the renal protective effect of daphnetin against ethylene glycol (GC)-induced hyperoxaluria via altering the gut microbiota. GC (1% v/v) was used for the induction of hyperoxaluria in the rats and the rats were received the oral administration of daphnetin (5, 10 and 15 mg/kg). The body and renal weight were assessed. Urine, renal, inflammatory cytokines, antioxidant, inflammatory parameters, and gut microbiota were appraised. Daphnetin effectually improved the body weight and reduced the renal weight. Its also remarkably boosted the magnesium, calcium, citrate level and suppressed the level of uric acid and oxalate formation. Daphnetin significantly (p < .001) ameliorate the level of urinary kidney injury molecule 1 (KIM-1), blood urea nitrogen (BUN), urea, serum creatinine (Scr), neutrophil gelatinase-associated lipocalin (NGAL) and uric acid along with inflammatory cytokines and inflammatory mediators. Daphnetin considerably repressed the malonaldehyde (MDA) level, protein carbonyl and improved the level of glutathione reductase (GR), superoxide dismutase (SOD), glutathione (GSH) and catalase (CAT). Daphnetin treatment considerably altered the microbial composition of different bacteria at phylum, genus and family level. Daphnetin significantly suppressed the Firmicutes relative abundance and boosted the Bacteroidetes relative abundance. Our result clearly indicated that daphnetin remarkably ameliorates the GC induced hyperoxaluria in rats via altering the oxidative stress, inflammatory reaction and gut microbiota. PRACTICAL APPLICATION: Nephrotoxicity is a serious health disease worldwide. We induce the renal toxicity in the experimental rats using the ethylene glycol and scrutinized the renal protective effect of daphnetin. Daphnetin considerably suppress the renal, urine parameters. For estimation the underlying mechanism, we estimated the gut microbiota in all group rats. Daphnetin remarkably altered the level of gut microbiota and suggesting the renal protective effect.

Chronic constant light exposure aggravates high fat diet-induced renal injury in rats.

Obesity-related kidney disease is now recognized as a global health issue, with a substantial number of patients developing progressive renal failure and end-stage renal disease. Interestingly, recent studies indicate light pollution is a novel environmental risk factor for chronic kidney disease. However, the impact of light pollution on obesity-related kidney disease remains largely unknown, with its underlying mechanism insufficiently explained. Renal hypoxia induced factor 1α (HIF1α) is critical in the development of glomerulosclerosis and renal fibrosis. The present study explored effects of constant light exposure on high fat diet (HFD) -induced renal injury and its association with HIF1α signal pathway. Thirty-two male Sprague Dawley rats were divided into four groups according to diet (HFD or normal chow diet) and light cycles (light/dark or constant light). After 16 weeks treatment, rats were sacrificed and pathophysiological assessments were performed. In normal chow fed rats, constant light exposure led to glucose abnormalities and dyslipidemia. In HFD fed rats, constant light exposure exacerbated obesity, glucose abnormalities, insulin resistance, dyslipidemia, renal functional decline, proteinuria, glomerulomegaly, renal inflammation and fibrosis. And, constant light exposure caused an increase in HIF1α and a decrease in prolyl hydroxylase domain 1 (PHD1) and PHD2 expression in kidneys of HFD-fed rats. Then, we demonstrated that BMAL1 bound directly to the promoters of PHD1 in mouse podocyte clone 5 cell line (MPC5) by ChIP assays. In conclusion, chronic constant light exposure aggravates HFD-induced renal injuries in rats, and it is associated with activation of HIF1α signal pathway.

Protective Effects of Hesperetin Against Lipopolysaccharide-induced Acute Renal Injury in Rat

Protective Effects of Hesperetin Against Lipopolysaccharide-induced Acute Renal Injury in Rat

Angiotensin 1–7 mitigates rhabdomyolysis induced renal injury in rats via modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme‑oxygenase-1 signaling pathways

AimsRhabdomyolysis (RM) is a critical condition with a high mortality rate, but effective management is still deficient. Till date, there are no studies that have addressed the effect of angiotensin 1–7 in this condition, hence, the rationale of this study was to evaluate the potential protective effect of Angiotensin 1–7 (Ang1–7), on rhabdomyolysis (RM) induced kidney injury in rats and detecting the underlying mechanistic insights. Main methodsForty adult male albino rats were divided into groups; the control group, RM group, RM+Ang1-7 group, and RM+Ang1-7+ A779 group. Sera and urine samples were collected for analysis of renal and muscle injury markers. Kidney tissues were taken for estimation of oxidative, inflammatory, and apoptotic markers as well as angiotensin-II (Ang II) and Ang1–7. Renal histology and expression of inducible nitric oxide synthase-1 (iNOS), real-time PCR for angiotensin-converting enzyme-2 (ACE-2), nuclear erythroid factor-2 (Nrf-2), Toll like receptor 4 (TLR-4) and NF-kB in kidney tissues were also measured. Key findingsInduction of RM caused renal oxidative stress injury, inflammation, apoptosis and marked deterioration in kidney functions as well as reduction of Ang1–7 and raised Angiotensin-II level in kidney tissues. Administration of Ang1–7 to the RM group reversed all the affected parameters which were blocked by A779 administration (Mas receptor blocker). SignificanceWe concluded that Ang1–7 could be a potential therapeutic agent that could mitigate RM-induced renal injury. The underlying mechanisms may involve Stimulation of the ACE-2/Ang1–7/MasR axis and modulation of TLR-4/NF-kB/iNOS and Nrf-2/heme‑oxygenase -1 pathways.

Formononetin Ameliorates Renal Dysfunction, Oxidative Stress, Inflammation, and Apoptosis and Upregulates Nrf2/HO-1 Signaling in a Rat Model of Gentamicin-Induced Nephrotoxicity.

Gentamicin (GEN) is a bactericidal aminoglycoside known to cause nephrotoxicity. Formononetin (FN) is a potent flavonoid that exhibits numerous promising pharmacological activities. In this study, we have assessed the nephroprotective efficacy of FN against GEN-induced renal injury in rats. Rats were orally administered with FN (60 mg/kg/day, for 2 weeks) and were co-treated with intraperitoneal (i.p.) injection of GEN (100 mg/kg/day) during the days 8–14. GEN-treated rats demonstrated increased urea and creatinine levels in serum associated with marked histopathological changes in the kidney. Malondialdehyde (MDA) and protein carbonyl contents were elevated, whereas glutathione concentration and catalase and superoxide dismutase activities were lowered in GEN-administered rats. The FN largely prevented tissue damage, attenuated renal function, reduced MDA and protein carbonyl, and enhanced antioxidant capacity in the kidney of GEN-administrated animals. The kidney of GEN-treated rats demonstrated elevated Bax and caspase-3 protein expression, accompanied by lowered Bcl-2 protein expression, an effect that FN attenuated. Moreover, FN treatment caused upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) expression in renal tissue of GEN-intoxicated animals. Collectively, FN protects against GEN-caused renal damage via exhibiting antioxidant, anti-inflammatory, and antiapoptotic activities and augmenting Nrf2 signaling, suggesting FN as a promising agent for preventing drug-induced organ damage.

Nigella Sativa Can Reverse Statin‐Induced Renal Injury in Rats: An Ultrastructural Study

Introduction and HypothesisAtorvastatin (ATO) and its siblings in the statin drug class are widely prescribed as a lipid lowering agent. However, ATO in high doses can induce renal toxicity via oxidative stress. Thymoquinone (TQ), an extractive of Nigella sativa,is a natural antioxidant that has been shown to protect the kidney via its anti‐inflammatory effects. The aim was to study the anti‐inflammatory effect of posttreatment TQ and whether it could reverse the ATO‐induced oxidative injury to the rat kidney.MethodsWe used 4 groups of adult male Sprague Dawley rats (control; TQ‐treated; ATO‐post treated; ATO‐ post treated plus TQ‐treated). Each group was formed of 10 rats. Ultrastructural, and morphometric analyses of the rat kidneys were performed. Statistical analysis was done using SPSS. One‐way analysis of variance (ANOVA) and post hoc tests (Bonferroni test) were used to compare the means of different groups, expressing data as mean ± standard deviation (SD) and P values of less than 0.01 were expected to be significant.ResultsMorphometric analyses of the ultrastructural examination revealed that the histopathological changes induced by post treatment ATO has improved in the ATO/TQ‐treated group compared to the ATO‐ post treated group.ConclusionPosttreatment TQ appears to reduce and reverse renal injury due to ATO‐induced oxidative stress. TQ can potentially play a role in alleviating side effects in patients with kidney disease who are being treated with high dose of atorvastatin.

Bone marrow mesenchymal stem cells attenuate pyroptosis lipopolysaccharide-induced renal injury rats

To investigate the effect and mechanism of bone marrow mesenchymal stem cell (BMSC) on pyroptosis of rats with kidney injury. Bone marrow of 4-5 week-old female Sprague-Dawley (SD) rats was isolated in vitro and BMSC was obtained. The third generations of BMSC were used to further experiments. Fifteen 6 week-old SD rats were cluster-randomized divided into control group, kidney injury group and BMSC group (5 rats in each group). Rats in kidney injury group were injected with lipopolysaccharide (LPS) 1 mg/kg via tail vein; the control group was given the same amount of normal saline. BMSC group was injected with 0.5 mL BMSC (including 2×106 BMSC) via tail vein after modeling; the kidney injury group received the same amount of normal saline. On day 3 after these injections, serum creatinine (SCr) was detected by picric acid method, and blood urea nitrogen (BUN) was detected by diacetyl monoxime. The levels of cystatin C (Cys C), interleukins (IL-1β and IL-18) in blood were detected by enzyme-linked immunosorbent assay (ELISA). The rats were then sacrificed and their kidneys were removed for subsequent detection. The mRNA expression levels of NOD-like receptor protein 3 (NLRP3) and cysteinyl aspartate-specific protease-1 (caspase-1) of kidney were detected by quantificational real-time quantitative polymerase chain reaction (qRT-PCR). The protein expression levels of NLRP3 and caspase-1 of kidney were detected by Western blotting. In vitro, after bone marrow cell suspension was cultured for 24 hours, a large number of round adherent cells and suspended cells appeared in each culture flask. After 4-5 days of culture, a large number of long spindle cells adhered to the wall, and there were still obvious impurity cells. After trypsin digestion and passage to the third generation, the long spindle adherent cells grew mainly in the culture flask and were basically purified as BMSC. In vivo, compared with the control group, the levels of SCr, BUN, Cys C, IL-1β and IL-18 in kidney injury group were increased [SCr (μmol/L): 85.22±2.29 vs. 21.80±0.59, BUN (mmol/L): 11.50±0.64 vs. 5.86±0.83, Cys C (mg/L): 0.13±0.01 vs. 0.11±0.02, IL-1β (ng/L): 31.49±1.42 vs. 4.74±0.49, IL-18 (ng/L): 29.01±1.95 vs. 1.52±0.03, all P < 0.05]. The mRNA and protein expression levels of NLRP3, caspase-1 were significantly increased [NLRP3 mRNA (2-ΔΔCt): 3.635±0.296 vs. 1.000±0.002, caspase-1 mRNA (2-ΔΔCt): 4.020±0.228 vs. 1.001±0.003; NLRP3 protein (NLRP3/β-actin): 1.560±0.868 vs. 0.902±0.036, caspase-1 protein (caspase-1/β-actin): 1.392±0.097 vs. 0.895±0.046, all P < 0.05]. Compared with kidney injury group, the levels of SCr, BUN, IL-1β and IL-18 in BMSC group were significantly decreased [SCr (μmol/L): 51.64±3.84 vs. 85.22±2.29, BUN (mmol/L): 9.90±0.46 vs. 11.50±0.64, IL-1β (ng/L): 24.20±1.45 vs. 31.49±1.42, IL-18 (ng/L): 12.97±1.25 vs. 29.01±1.95, all P < 0.05]. The mRNA and protein expression levels of NLRP3, caspase-1 were significantly decreased [NLRP3 mRNA (2-ΔΔCt): 1.488±0.136 vs. 3.635±0.296, caspase-1 mRNA (2-ΔΔCt): 1.643±0.143 vs. 4.020±0.228; NLRP3 protein (NLRP3/β-actin): 1.227±0.053 vs. 1.560±0.868, caspase-1 protein (caspase-1/β-actin): 1.159±0.107 vs. 1.392±0.097, all P < 0.05]. In vivo, BMSC may attenuate pyroptosis in LPS-induced kidney injury rats.

Olanzapine-Induced Therapeutic Hypothermia Attenuates Renal Injury in Rats after Asphyxial Cardiac Arrest and Resuscitation.

Return of spontaneous circulation (ROSC) through cardiopulmonary resuscitation (CPR) after cardiac arrest (CA) causes post-cardiac arrest syndrome (PCAS) due to dysfunction in various organs, which provokes acute kidney injury because of renal ischemia-reperfusion injury. Therapeutic hypothermia (TH) can reduce PCAS after CA and ROSC. However, it needs to be more sophisticated and effective. Hence, we aimed to elucidate the protective effects of olanzapine-induced TH against renal injury in asphyxial CA-induced rats. Every rat’s body temperature was maintained at 33 °C for 6 h after administering olanzapine post-CA and ROSC. Olanzapine-induced TH dramatically increased the survival rate of the rats and ameliorated renal tissue damage. Moreover, it suppressed oxidative stress responses through preservation of mitochondrial function and endoplasmic reticulum stress as the main contributor of oxidative stress. Notably, these actions of olanzapine-induced TH were mediated through the Sirt3-related signaling pathway, including the maintenance of Sirt3 and FOXO3a protein expression and the activation of AMPKα and superoxide dismutase 1 (SOD2, a mitochondrial antioxidant). This study is the first to disclose the protective effects of olanzapine-induced TH against renal injury after CA and ROSC, suggesting that olanzapine-induced TH could be utilized for treating CA followed by ROSC.

Protective Effects of Naringenin from Citrus sinensis (var. Valencia) Peels against CCl4-Induced Hepatic and Renal Injuries in Rats Assessed by Metabolomics, Histological and Biochemical Analyses.

Citrus fruits are grown worldwide for their special nutritive and several health benefits. Among citrus bioactives, naringenin, a major flavanone, exhibits a potential hepatoprotective effect that is not fully elucidated. Herein, serum biochemical parameters and histopathological assays were used to estimate the hepatoprotective activity of naringenin, isolated from Citrus sinensis (var. Valencia) peels, in CCl4-induced injury in a rat model. Further, GC–MS-based untargeted metabolomics was used to characterize the potential metabolite biomarkers associated with its activity. Present results revealed that naringenin could ameliorate the increases in liver enzymes (ALT and AST) induced by CCl4 and attenuate the pathological changes in liver tissue. Naringenin decreased urea, creatinine and uric acid levels and improved the kidney tissue architecture, suggesting its role in treating renal disorders. In addition, naringenin increased the expression of the antiapoptoic cell marker, Bcl-2. Significant changes in serum metabolic profiling were noticed in the naringenin-treated group compared to the CCl4 group, exemplified by increases in palmitic acid, stearic acid, myristic acid and lauric acids and decrease levels of alanine, tryptophan, lactic acid, glucosamine and glucose in CCl4 model rats. The results suggested that naringenin’s potential hepato- and renoprotective effects could be related to its ability to regulate fatty acids (FAs), amino acids and energy metabolism, which may become effective targets for liver and kidney toxicity management. In conclusion, the current study presents new insights into the hepato- and renoprotective mechanisms of naringenin against CCl4-induced toxicity.

Atorvastatin Exerts Protective Effect on Cardiopulmonary Bypass Induced Renal Injury in Rats via PPAR-γ.

To investigate the protective effect and possible mechanism of atorvastatin pretreatment on renal function after cardiopulmonary bypass (CPB) in rats. Twenty-four adult male Sprague-Dawley (SD) rats randomly were divided into three groups: Sham operation group, CPB group, and administration group (N = 8 in each group). The caudal artery and right jugular vein were used to establish the CPB circuit for the CPB and administration groups. Drugs were administered by oral gavage one week before the operation. All rats were executed for succeeding experiments 72h after the operation. Plasma levels of creatinine (Cre) and IL-8 at different time points and levels of TNF-α and MPO in renal tissue were detected by ELISA. Renal pathological changes were observed by HE staining. PPAR-γ expression was determined by immunohistochemistry and western blot. All rats survived the whole process without incident. Renal function of rats undergoing CPB was impaired to varying degrees based on the plasma Cre concentration, and atorvastatin pretreatment alleviated this effect. The concentrations of six inflammatory cytokines (IL-1β, IL-6,IL-8, IFN-γ,TNF-α, and MPO) were significantly elevated after CPB procedure, while atorvastatin pretreatment ameliorated the inflammatory condition caused by CPB. Further analysis showed that in both HK-2 cells and renal tissues, atorvastatin promoted the expression of PPAR-γ. Atorvastatin pretreatment exerted protective effect on CPB-associated kidney injury and inflammation in rats. The activation of PPAR-γ may contribute to the protective effect of Atorvastatin.

Vanillin attenuates thioacetamide-induced renal assault by direct and indirect mediation of the TGFβ, ERK and Smad signalling pathways in rats.

Inflammation and fibrosis are two pathological features of chronic kidney disease (CKD). Renal fibrosis is considered to be one of the most important conditions, as it may be the result of excessive extracellular matrix protein production and deposition, or prolonged exposure to nephrotoxic substances or drugs. Unfortunately, no suitable therapies or medications are currently available to prevent renal fibrosis. We conducted this study for the evaluation of the protective potential of vanillin by reversing TAA (250 mg/kg TAA for 6 weeks) induced renal injury in rats. The concentrations of the proteins tumour necrosis factor alpha (TNFα), interleukin-6 (IL-6), extracellular signal regulated kinase 1/2 (Erk1/2), and transforming growth factor beta-1 (TGF-β1) in kidney tissues were assessed using ELISA. Kidney Injury Molecule-1 (KIM-1) and mothers against decapentaplegic homologue 2, 3 (SMAD 2, 3) expressions were evaluated using real time PCR. We also estimated the expression of α-smooth muscle actin (α-SMA) using immunohistochemistry. Treatment with vanillin (100 mg/kg) significantly ameliorated kidney Injury and improved the kidney function. Vanillin treatment also significantly decreased the malondialdehyde (MDA) content, and elevated glutathione peroxidase (GPx) and catalase (CAT) activities in kidney tissues. Vanillin also reduced α-SMA renal expression and TNFα, IL-6, TGF-β1, and Erk1/2 renal levels. Vanillin significantly decreased the expression of the genes encoding KIM-1 and SMAD 2, 3 and ameliorated histological abnormalities in kidney architecture. Our molecular docking findings showed that vanillin has a good binding mode inside TGF-β type I receptors (ALK5) biding site.

Trans-resveratrol alleviates hepatic and renal injury in γ-irradiated rats.

Although ionizing radiation (IR) has been of immense value to human life due to its involvement in several fields, it doesn't eliminate that exposure to IR results in an array of biological consequences, including oxidative stress, inflammation, and death. Thus, this study aimed to explore the curative effect of trans-Resveratrol (t-Res) on hepatic and renal injury in a rat model exposed to single and fractionated doses of γ-rays. Rats exposed to a single dose of IR (6Gy, as an acute effect) or a fractionated dose of IR (2Gy/time/3days, day after day; to imitate a chronic impact) were treated with t-Res. Then, the radio-protective effect of t-Res was investigated via biochemical and histological estimations in the liver and kidney of rats in the different groups. The data displayed a significant amelioration in biochemical and histological indices in the liver and kidney of rats exposed to IR doses and treated with t-Res. Particularly, t-Res reduced the oxidative stress milieu through decreasing HIF-1α, ROS, and MDA levels associated with increased CAT activity and Nrf-2 gene expression. Also, t-Res improved the inflammatory status via a decrease in TNF-α, NF-κB, SOCS-3, and HSP-70 genes expression linked with elevations in SIRT-1 and P53 genes expression. It could be concluded that t-Res had hepatoprotective and renoprotective effects against the deleterious consequences of γ-rays exposure due to its antioxidant and anti-inflammatory properties.

Effect of hyperphosphatemia on impairment of vascular function in adenine-induced renal injury in rats

We reported that vascular function in adenine-induced renal injury rats was impaired mediated by increase in plasma indoxyl sulfate concentration. It is known that hyperphosphatemia leads to calcification and atherosclerosis. In the present study, we examined effect of hyperphosphatemia on vascular dysfunction in adenine-induced renal injury in anesthetized rats. Renal injury was induced by feeding 0.75% adenine diet for 4 weeks. Lanthanum carbonate was treated with gavage after 2 weeks induced adenine. Treatment with lanthanum carbonate significantly decreased in plasma phosphorus concentration in adenine rats. N-nitro-L-arginine (L-NA) potentiated the ACh-induced depressor response in normal-diet. However, L-NA failed to potentiate the response in adenine rats or lanthanum-treated rats. Sodium nitroprusside (SNP)-induced depressor response in adenine rats was significantly smaller than that in normal rats. Lanthanum carbonate tended to recover impairment of SNP-induced depressor responses in adenine rats. These findings suggest that hyperphosphatemia is partially related to impairment of smooth muscle function rather than that of endothelial function in adenine rats.

Taurine Prevents AFB1-Induced Renal Injury by Inhibiting Oxidative Stress and Apoptosis.

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins, which can cause serious kidney damage after ingestion. Taurine protects the kidney, an effect related to its antioxidation and anti-apoptotic actions. In the present study, taurine was administered to detect the protective effect and mechanism of taurine on AFB1-induced renal injury in rats. The results show that taurine ameliorated the increase in serum blood urea nitrogen (BUN), blood creatinine (CRE), blood uric acid (UA), cystatin c (Cys-c), and urinary protein and AKP levels. Taurine also inhibits the content of superoxide dismutase (SOD), total antioxidant capacity (T-AOC), catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-Px), succinate dehydrogenase (SDH), and the mRNA expression of SOD, nicotinamide adenine dinucleotide phosphate-quinine oxidoreductase 1 (NQO1), γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), and glutamate cysteine ligase catalytic (GCLC) in rat kidney tissue. The apoptotic rate of renal cells was decreased by taurine through inhibition of a mitochondrial mechanism. In summary, we found that taurine prevents AFB1-induced renal injury via enhanced antioxidant ability and mitochondrial-dependent apoptosis.

Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats: Role of oxidative stress, inflammation and caspase-3

Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer. Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activity present in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate the nephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistar albino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats received boldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip) was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidney index. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities and tumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Inducible nitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicity induced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, and decreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at both boldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathological findings supported biochemical findings. Taken together these findings indicate that boldine has promising protective effect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations and by alleviating caspase 3 expression.