The Nephroprotective Effect of Clove Oil (Oleum Caryophylli) Against Levofloxacin Toxicity in Rats

Background: Levofloxacin is a fluoroquinolone antibiotic that has broad-spectrum antimicrobial activity, but it may induce kidney dysfunction. Clove oil (Oleum caryophylli) has antioxidant properties that may alleviate levofloxacin toxicity. This study aimed to examine the protective effect of clove oil on levofloxacin-induced nephrotoxicity in rat animal models. Methods: A total of 24 male rats were divided into 6 groups. One group did not receive levofloxacin to serve as the control. The treatment groups received a single daily administration of levofloxacin (93 mg/kg) with either placebo or clove oil (10 mg/kg, 25 mg/kg, or 50 mg/kg per body weight) pre-treatment. Another group received Curcuma extract pre-treatment as a comparison. Blood samples were withdrawn after 28 days of treatment to measure serum biomarkers (urea and creatinine), and the kidneys were removed to measure renal Malondialdehyde (MDA) and histopathological analysis. Results: The results showed that clove oil pre-treatment at a dose of 10 mg/kg was able to reduce renal MDA and serum biomarker levels (P<0.05). The effect was similar to that found in Curcuma-treated rats. In addition, clove oil (10 mg/kg) was also found to ameliorate renal histopathological damage due to levofloxacin. Conclusion: Based on biomarker and histopathological analysis, clove oil pre-treatment in rats provides a nephroprotective effect against levofloxacin toxicity.

Epigenetic mechanisms of nephroprotection in diabetic nephropathy: focus is on sirtuin-1

Numerous studies have shown the critical role of sirtuin-1 deacetylase (SIRT1) in the protection of renal cells from endogenous and exogenous stresses. A protective role for SIRT1 has been established in both podocytes and renal tubular cells in many kidney diseases, including diabetic nephropathy (DN). SIRT1 has also been shown to have nephroprotective effects in DN, in part through the deacetylation of transcription factors involved in disease pathogenesis, such as p53, FOXO, RelA / p65NF-KB, STAT3, and PGC1a / PPARy. Recently, it was found that podocyte-specific overexpression of SIRT1 attenuates proteinuria and kidney damage in an experimental model of DN, suggesting the possibility of using SIRT1 as a potential target for the treatment of kidney disease. In addition, SIRT1 agonists such as resveratrol and BF175 have been shown to reduce diabetic kidney damage in several experimental animal models. It has also been shown that puerarin, a Chinese herbal medicine, activates SIRT1, providing nephroprotection in a mouse model of DN. In addition to SIRT1 agonists, inhibitors of bromodomain, in particular, MS417, also have a nephroprotective effect. These results suggest that SIRT1 agonists and bromodomain inhibitors may be new potential therapeutic agents that slow the progression of DN.

Nephroprotective Effect of the Virgin Olive Oil Polyphenol Hydroxytyrosol in Type 1-like Experimental Diabetes Mellitus: Relationships with Its Antioxidant Effect

The aim of this study was to determine whether hydroxytyrosol administration prevented kidney damage in an experimental model of type 1 diabetes mellitus in rats. Hydroxytyrosol was administered to streptozotocin-diabetic rats: 1 and 5 mg/kg/day p.o. for two months. After hydroxytyrosol administration, proteinuria was significantly reduced (67–73%), calculated creatinine clearance was significantly increased (26–38%), and the glomerular volume and glomerulosclerosis index were decreased (20–30%). Hydroxytyrosol reduced oxidative and nitrosative stress variables and thromboxane metabolite production. Statistical correlations were found between biochemical and kidney function variables. Oral administration of 1 and 5 mg/kg/day of hydroxytyrosol produced an antioxidant and nephroprotective effect in an experimental model of type 1-like diabetes mellitus. The nephroprotective effect was significantly associated with the systemic and renal antioxidant action of hydroxytyrosol, which also influenced eicosanoid production.

Effect of Metformin on the Kidney Histology of Rats in Gentamicin Induced Toxicity

Acknowledgment: We are indebted to Dr. Rashad Hussain from department of animal sciences, Quaid-i-Azam University, Islamabad for his consistent support and guidance for the write up of this manuscript. Study’s background and aim: Metformin, an oral antidiabetic agent has been studied in the past for its protective effects in aminoglycoside induced renal injuries. We hypothesized that the use of metformin may be protective in the aminoglycoside mediated acute renal failure. We thus tried two doses of metformin (M1; 75mg/kg/day) (M2; 150mg/kg/day) to evaluate this preventive potential on gentamicin induced acute renal failure in rats. Study Design: Randomized controlled trial Place of Study: Animal House of National Institute of Health Islamabad/ Department of Pharmacology, AL Nafees Medical College and Hospital, Islamabad, duration was 1stAugust 2018 to 31stJanuary 2019. Materials and Methods: The rats were divided into three main groups (n=10) kept under similar conditions for food and temperature. Renal failure was induced by injecting gentamicin (80mg/kg/day) intraperitonealy (ip) for eight days with simultaneous administration of oral metformin for 28 days.Slides of rats’ kidneys were prepared for histological comparison at the last day of study. Results: In gentamicin induced renal failure and simultaneous administration of metformin, the histological findings of rat kidneys showed remarkable tissue necrosis in control group and prevention in metformin treated groups. Conclusion: Based on the histological results of our study it was concluded that metformin at a dose of 150mg/kg showed a nephroprotective effect in gentamicin induced renal injuries in Sprague-Dawley rats. Keywords: Metformin, Gentamicin, Nephrotoxicty, Renal injuries, Nephroprotective effect

R. vesicarius L. exerts nephroprotective effect against cisplatin-induced oxidative stress

Background Cisplatin is an outstanding anticancer drug, but its use has been decreased remarkably due to sever nephrotoxicity. R. vesicarius L. is a leafy vegetable that is evident with anti-angeogenic, anti-inflammatory, anti-proliferative, hepatoprotective, and nephroprotective potential. Therefore, this study was designed to inspect its methanol extract (RVE) for possible nephroprotective effect. Methods Primarily, in vitro antioxidant activity of RVE was confirmed based on 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging aptitude. Thereafter, Swiss Albino male mice were treated with cisplatin (2.5 mg/kg) for 5 successive days to induce nephrotoxicity. Recovery from nephrotoxicity was scrutinized by treating the animals with RVE (25, 50, and 100 mg/kg) intraperitoneally (i.p.) for the next 5 consecutive days. After completion of treatment, mice were sacrificed and kidneys were collected. Part of it was homogenized in sodium phosphate buffer for evaluating malondialdehyde (MDA) level, another part was used to evaluate gene (NQO1, p53, and Bcl-2) expression. Moreover, the hydrogen peroxide (H2O2) neutralizing capacity of RVE was evaluated in HK-2 cells in vitro. Finally, bioactive phytochemicals in RVE were determined using gas chromatography–mass spectrometry (GC-MS). Results RVE showed in vitro antioxidant activity in a dose-dependent fashion with 37.39 ± 1.89 μg/mL IC50 value. Treatment with RVE remarkably (p < 0.05) decreased MDA content in kidney tissue. Besides, the expression of NQO, p53, and Bcl-2 genes was significantly (p < 0.05) mitigated in a dose-dependent manner due to the administration of RVE. RVE significantly (p < 0.05) reversed the H2O2 level in HK-2 cells to almost normal. From GC-MS, ten compounds including three known antioxidants “4H-Pyran-4-one, 2, 3-dihydro-3,5-dihydroxy-6-methyl-”, “Hexadecanoic acid”, and “Squalene” were detected. The extract was rich with an alkaloid “13-Docosenamide”. Conclusion Overall, RVE possesses a protective effect against cisplatin-induced kidney damage.

Nephroprotective role of diosgenin in gentamicin-induced renal toxicity: biochemical, antioxidant, immunological and histopathological approach

Background Aminoglycoside antibiotics, gentamicin (GM) owns the utmost nephrotoxic potential than other antibiotics from the same category. To the other side, diosgenin (DG) showed the antioxidant and anti-inflammatory property. Results The present study was aimed to explore the nephroprotective effect of diosgenin on gentamicin-induced renal toxicity in Wistar rats. Wistar albino rats were divided into six groups (n = 6): Normal control (NC), Nephrotoxicity control (GM), DG (20 mg/kg), DG (40 mg/kg), DG (80 mg/kg), accordingly. After the treatment, the nephroprotective effects of DG were assessed by measuring serum levels of creatinine (Cr), blood urea nitrogen (BUN), total proteins (TP), albumin and urea levels. Urine volume, proteins, electrolyte levels, creatinine clearance were also evaluated in urine samples. Oxidative stress was evaluated through the measurement of antioxidant stress markers in the kidney tissue. Changes in body weight and kidney weight were also recorded along with a histopathological examination of kidney sections. For evaluation of inflammation, TNF-α and IL-1β levels were measured in the blood serum using ELISA kits. GM intoxication induced elevated serum creatinine, BUN, urea, albumin and TP levels, urine electrolytes levels, pro-inflammatory cytokines, antioxidant parameters which were found to be decreased significantly in a dose-dependent manner in rat groups received DG which was also evidenced by the histological observations. Conclusion DG showed a significant nephroprotective effect in a dose-dependent manner by ameliorating the GM induced nephrotoxicity in Wistar rats.