Evaluation of traditionally used royal jelly (RJ) for the management of hepato-renal damage and gastrointestinal ulcerations caused by diclofenac. Methods: Forty adult male Wistar rats were allocated into four groups. Rats of the 1 st group received only saline and served as normal group. The remaining 3 groups received diclofenac (50 mg/kg/day, I.P.) for 7 days. Group 2 served as diclofenac-control group. Groups 3 and 4 received RJ (150 and 300 mg/kg/day, P.O.) respectively for 30 days. Twenty-four hours after the last treatment, blood samples were collected, rats were sacrificed, and livers, kidneys, stomachs & intestines were harvested. Stomachs and intestines were tested for ulcer counts. Serum levels of AST, ALT, creatinine and urea were investigated. Hepatic, renal, gastric and intestinal tissue contents of myeloperoxidase (MPO) and prostaglandin-E2 (PGE2) were measured. Histopathological examinations were also performed followed by immunohistochemical determination of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression. Results: Diclofenac administration caused significant deterioration of all the above mentioned parameters. RJ improved hepatic and renal functions. Gastric and intestinal ulcer counts were significantly ameliorated. Hepatic, renal, gastric and intestinal tissue PGE-2 contents and COX-2 expression were significantly elevated. RJ also significantly reduced MPO content and iNOS expression as compared to diclofenac-control group. Improvements of the histopathological pictures of hepatic, renal, gastric and intestinal tissues were also apparent. Conclusion:The study demonstrates promising protective effects of RJ against diclofenac-induced hepato-renal damage and gastrointestinal ulceration in rats.

AIM:The present study investigated the protective effect of the phytoestrogen, genistein (GEN), against (CP)-induced acute hepatotoxicity in rats.MATERIAL AND METHODS:Male adult rats were randomly assigned into five groups. Normal control group received the vehicles; CP group received a single dose of CP (200 mg/kg, i.p). The other three groups received subcutaneous GEN at doses of 0.5, 1 and 2 mg/kg/day, respectively, for 15 consecutive days prior CP injection. Sera and liver tissues were collected forty-eight hours after CP injection for assessment of liver function enzymes (ALT and AST) in rat sera, the hepatic oxidative/nitrosative biomarkers (GSH, MDA and NOx), hepatic interleukin-1β, and myeloperoxidase activity. Immunohistochemistry of cyclooxygenase-2 and histopathological examination of liver tissues were also conducted.RESULTS:The CP-induced acute liver damage was evidenced by elevated serum ALT and AST accompanied by increased hepatic oxidative stress and inflammatory biomarkers. Immunohistochemical outcomes revealed hepatic cyclooxygenase-2 expression in CP group with distortion of liver architecture. GEN-pretreatment significantly ameliorated the deterioration of liver function and exerted significant anti-oxidant and anti-inflammatory activity with a marked decline in hepatic cyclooxygenase-2 expression in a dose dependent-manner.CONCLUSION:The present study demonstrated that the antioxidant and anti-inflammatory activities of GEN might contribute to its protective effects against CP-induced liver damage.

No abstract

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome ultimately occurs as a complication of acute or chronic liver failure; accompanied by hyperammonemia. This study aimed to evaluate the potential of biopropolis as a hepato and neuroprotective agent using thioacetamide (TAA)-induced acute HE in rats as a model. Sixty Wistar rats were divided into five groups: Group 1 (normal control) received only saline and paraffin oil.Group 2 (hepatotoxic control) received TAA (300 mg/kg, once). Groups 3, 4 and 5 received TAA followed by vitamin E (100 mg/kg) and biopropolis (100 and 200 mg/kg), respectively, daily for 30 days. Evidences of hepatic encephalopathy were clearly detected in TAA-hepatotoxic group including significant elevation in the serum level of ammonia, liver functions, increased oxidative stress in liver and brain, apoptotic DNA fragmentation and overexpression of iNOS gene in brain tissue. The findings for groups administered biopropolis, highlighted its efficacy as a hepato and neuro-protectant through improving the liver functions, oxidative status and DNA fragmentation as well as suppressing the brain expression of iNOS gene. In conclusion, bioproplois, at a dose of 200 mg/kg/day protected against TAA-induced HE through its antioxidant and antiapoptotic influence; therefore, it can be used as a protective natural product.Keywords: Biopropolis; hepatic encephalopathy; thioacetamide; iNOS; vitamin E. IntroductionHepatic encephalopathy (HE) is a neuropsychiatric syndrome resulting from acute or chronic liver failure (Lizardi-Cervera et al. 2003). HE affects a huge number of patients worldwide leading to a mortality rate of 50 to 90% (Raghavan and Marik 2006). HE causes a wide range of clinical manifestations, including psychomotor dysfunctions, sensory abnormalities, poor concentration, increased reaction time and impaired memory. Patients commonly develop stupor, coma and death in severe cases.The mechanism of HE has not been fully explained. However, hyper-ammonemia has been suggested to play the main role in HE pathogenesis and to be responsible for the direct and indirect alterations in cerebral metabolism and hence encephalopathy (Frederick 2011;Mustafa et al. 2013).Thioacetamide (TAA) is used to induce an experimental rat model mimicking acute hepatic failure and HE. This model has been validated to be a satisfactory model of HE (Avraham et al. 2006). TAA undergoes extensive metabolism to highly reactive metabolites that binds to liver macromolecules resulting in hepatic necrosis, hyperammonemia (Swapna et al. 2006) and extensive oxidative stress (Sathyasaikumar et al. 2007). Studies demonstrated that centrilobular necrosis is apparent after single dose of TAA, while cirrhosis, liver cell adenomas and liver cancer usually develop after chronic administration (Waters et al. 2005).Oxidative stress has long been involved in the pathogenesis of acute and chronic liver damage in many conditions such as toxin exposures, bile duct obstruction, excess alcoholism, liver ischemia, and viral inf...

Background and purpose: The clinical use of the chemotherapeutic drug, doxorubicin (DXR), is significantly limited by its extensive multi-organ toxicity. Dipeptidyl peptidase-4 (DPP4) is over-expressed in oxidative stress, inflammation and apoptosis. DPP4 inhibitors have proven pleiotropic effects. The study investigates the protective effects of some DDP4 inhibitors; namely, saxagliptin (SAX) and vildagliptin (VIL) against DXR-induced nephrotoxicity in rats. Experimental approach: Forty rats were divided into 4 groups. Group I served as normal control. Nephrotoxicity was induced in the remaining 3 groups by single-DXR injection (15 mg/kg, i.p.). Groups III and IV administered oral SAX (10 mg/kg) and VIL (10 mg/kg) for 2 weeks. Findings/Results: DXR-control rats showed deteriorated renal functions, elevated renal inflammatory parameters (tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and inducible nitric oxide synthase (iNOS)), up-regulated nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome and significant tubulointerstitial injury manifested by elevated neutrophil gelatinase-associated lipocalin concentration and distorted renal histopathological pictures. Immunohistochemical studies showed increased iNOS and Bax positivity in renal tissues of DXR-control rats. Treatment with SAX and VIL significantly attenuated DXR-induced nephrotoxicity via alleviation of all the above-mentioned parameters when compared to DXR-control rats. Conclusion and implications: The study elucidated the possible mechanisms beyond DXR-induced nephrotoxicity to be through inflammation plus tubulointerstitial injury. DXR nephrotoxicity has been linked to TNF-α, IL-1β, and NLRP3 inflammasome up-regulation and iNOS expression. The protective role of SAX and VIL in mitigating the tubular injury and inflammatory effects of DXR on renal tissues has been tested and proved.