Hepatoprotective effects of vildagliptin mitigates lung biochemical and histopathological changes in experimental hepatopulmonary syndrome model in rat.

Hepatopulmonary syndrome (HPS) is a liver disease-induced pulmonary complication manifested with arterial hypoxemia. Hepatic cholestasis, encountered in several clinical situations, leads to biliary cirrhosis and HPS, both of which are best reproduced by rat common bile duct ligation (CBDL). Experience from liver transplantation suggests hepatoprotective-based therapy would be most effective in HPS treatment Dipeptidyl peptidase-4 (DPP-4) enzyme is involved in different pathogenic mechanisms of liver diseases. Vildagliptin (Vild) is a DPP-4 inhibitor which possesses favorable anti-inflammatory, anti-oxidant and anti-fibrotic effects. The present work explored hepatoprotective mechanisms of Vild and their participation in its prophylactic effectiveness in HPS induced by CBDL in rats. Male Wistar rats weighing 220-280 g were allocated into 4 groups: normal control, sham, CBDL and CBDL + Vild groups. i.p. saline was administered to the first 3 groups and i.p. Vild (10 mg/kg/day) was given to the fourth group for 6 weeks starting 2 week before CBDL. CBDL produced liver fibrosis, arterial hypoxemia and decreased survivability of rats. It altered liver functions and induced oxidative stress, pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)], vasodilatory molecules [endothelin-1 (ET-1), and inducible and endothelial nitric oxide synthases] and angiogenesis-associated protein [vascular endothelial growth factor-A (VEGF-A)] in liver and lung. Vild ameliorated liver fibrosis, and improved hypoxemia and survivability of CBDL rats and reversed these biochemical alterations. Prophylactic Vild administration attenuated CBDL-induced HPS in rats via direct hepatoprotective effects in the form of anti-oxidant, anti-inflammatory, anti-angiogenic and anti-fibrotic effects beside inhibition of pathological intrahepatic vasodilatation.

Vildagliptin ameliorates intrapulmonary vasodilatation and angiogenesis in chronic common bile duct ligation-induced hepatopulmonary syndrome in rat.

INTRODUCTION: Experimental hepatopulmonary syndrome (HPS) is best reproduced in the rat common bile duct ligation (CBDL) model. Vildagliptin (Vild) is an anti-hyperglycemic drug that exerts beneficial anti-inflammatory, anti-oxidant and anti-fibrotic effects. Therefore, the present search aimed to explore the possible effectiveness of Vild in CBDL-induced HPS model. METHODS: Four groups of male Wistar rats which weigh 220-270 g were used, including the normal control group, the sham control group, the CBDL group and CBDL+Vild group. The first three groups received i.p. saline, while the last group was treated with i.p. Vild (10 mg/kg/day) from the 15th to 28th day of the experiment. RESULTS: CBDL decreased the survivability and body weight of rats, increased diameter of the pulmonary vessels, and altered the arterial blood gases and the liver function parameters. Additionally, it increased the pulmonary expressions of endothelin-1 (ET-1) and tumor necrosis factor-α (TNF-α) mRNA as well as endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor-A (VEGF-A) proteins. The CBDL rats also exhibited elevation of the pulmonary interleukin-6 (IL-6), dipeptidyl peptidase-4 (DPP-4) and nitric oxide (NO) levels along with reduction of the pulmonary total anti-oxidant capacity and glucagon-like peptide-1 (GLP-1) levels. Vild mitigated these alterations and improved the histopathological abnormalities caused by CBDL. CONCLUSION: Vild effectively attenuated CBDL-induced HPS through its anti-oxidant and anti-inflammatory effects along with its modulatory effects on ET-1/NOS/NO and TNF-α/IL-6/VEGF-A signaling implicated in the regulation of intrapulmonary vasodilatation and angiogenesis, respectively.

Ameliorative Effects of Zinc Oxide, in Either Conventional or Nanoformulation, Against Bisphenol A Toxicity on Reproductive Performance, Oxidative Status, Gene Expression and Histopathology in Adult Male Rats.

Bisphenol A (BPA) is a widely used endocrine disruptor that represents a significant risk to male reproductive function. Zinc (Zn) is vital for appropriate development of testes and to guarantee optimal testicular function and spermatogenesis. Our goal was to investigate if zinc oxide (ZnO), either in conventional or nanoformulation, could safeguard adult male rats' reproductive performance against the damaging effects of BPA. Signaling expression of CYP11A1 and Nrf-2 in the testis, testicular oxidant-antioxidant status, Bax/Bcl-2 apoptotic ratio, and histological examination of various reproductive organs were all evaluated. Twenty-eight adult male albino rats were divided randomly into 4 groups (7 animals each) including the control, BPA, conventional zinc oxide (cZnO) + BPA, and zinc oxide nanoparticles (ZnO-NPs) + BPA groups. The study was extended for 2 successive months. Our findings revealed strong negative effects of BPA on sperm cell characteristics such as sperm motility, viability, concentration and abnormalities. Additionally, BPA reduced serum levels of testosterone, triiodothyronine (T3), and thyroxine (T4). Also, it evoked marked oxidative stress in the testes; elevating malondialdehyde (MDA) and reducing total antioxidant capacity (TAC). BPA significantly downregulated testicular mRNA relative expression levels of CYP11A1 and Nrf-2, compared to control. Testicular apoptosis was also prompted by increasing Bax/ Bcl-2 ratio in testicular tissue. Histopathological findings in the testes, epididymis, prostate gland, and seminal vesicle confirmed the detrimental effects of BPA. Interestingly, cZnO and ZnO-NPs significantly alleviated all negative effects of BPA, but ZnO-NPs performed better. In conclusion, our findings point to ZnO, specifically ZnO-NPs, as a viable treatment for BPA-induced testicular dysfunction.

The protective effects of date seeds, in either conventional or nanoformulation, against bisphenol A-induced testicular toxicity: involvement of testicular expression of CYP11A1, Nrf-2 and Bax/Bcl-2 ratio.

Background: Bisphenol A (BPA), an endocrine-disrupting chemical (EDC), is ubiquitous in our environment and poses a significant threat to male fertility. Date seeds (DSs) are used in folk medicine due to their antioxidant activity. Aim: The purpose of this study was to assess the beneficial effects of DSs, whether in powder or nanoparticle form, against BPA-induced testicular oxidative challenges and apoptosis, aided by inspection of specific genes linked to fertility, oxidative stress and intrinsic mitochondrial pathway of apoptosis. Methods: Thirty-five adult male albino rats were equally divided into 5 groups including control, BPA, BPA + date seeds powder "DSP", BPA + date seed nanoparticle 1/10 (DSNP 1/10) and BPA + DSNP 1/20 groups. Results: TEM showed that the ball-mill method was effective to form DSNP with an average size of 20 nm. BPA significantly impaired sperm motility, morphology, viability and concentration. It also reduced serum testosterone levels and evoked marked oxidative stress in the testes. Additionally, serum levels of triiodothyronine and thyroxine were extremely reduced. Moreover, testicular mRNA relative expression levels of CYP11A1 and Nrf-2 were markedly downregulated. Testicular apoptosis was also promoted whereas Bax/Bcl-2 ratio was profoundly elevated. Histological pictures of the testes, epididymis, seminal vesicles and prostate confirmed the unfavorable effects of BPA. Surprisingly, we first demonstrated that DSs, specifically the nanoparticle form, strongly alleviated all of BPA's negative effects, with DSNP 1/20 achieving the best results. Conclusion: Therefore, DSNP in both doses could be regarded as an ideal candidate for abating the male reproductive challenges caused by BPA.

Comparative Effect of Allicin and Alcoholic Garlic Extract on the Morphology and Infectivity of Eimeria tenella Oocysts in Chickens.

Avian coccidiosis remains one of the major parasitic diseases that threaten the global poultry industry. Since prevention is superior to treatment, this study focuses on eliminating the infection outside the host. To determine their effect on the viability of Eimeria tenella oocysts in vitro, allicin and alcoholic garlic extract, which are natural, less toxic, and inexpensive products, were compared to KOH 5% (chemical disinfectant) using an in vitro culture system. Three concentrations of allicin (45, 90, and 180 mg/mL) and alcoholic garlic extract (90, 180, and 360 mg/mL, were used. Subsequently, destructive and sporulation-inhibiting effects on Eimeria oocysts were detected using light and electron microscopy. Young chickens were infected with treated sporulated oocysts to determine their effect on infectivity. After 7 days pi, the percentage of excreted oocysts (oocyst shedding) was determined, and the chickens were slaughtered for histopathological examination of the cecal tissues. Under an electron microscope, allicin at a concentration of 180 mg/mL and alcoholic garlic extract at a concentration of 360 mg/mL demonstrate a high oocysticidal activity with severe destruction of the oocyst wall and the appearance of pores. In addition, both concentrations directly affected the infectivity of sporulated oocysts by reducing the shedding of oocysts and the pathological lesions of infected young chickens. We concluded that the ability of Allicin and alcoholic garlic extract to eliminate Eimeria oocysts makes them superior to chemical disinfectants as a disinfectant.