Prophylactic and curative effects of Carica papaya Linn. pulp extract against carbon tetrachloride-induced hepatotoxicity in male rats.

Several chemicals and medications induce cellular damage in various organs of the body by activating reactive substances' metabolism leading to various pathological conditions including liver disease. In this study, we evaluated the prophylactic and curative effects of Carica papaya Linn. pulp water extract (PE) against CCl4-induced rat hepatotoxicity. Five groups of rats were created, control, PE, CCl4, (PE-CCl4): The rats were administered with PE pre and during CCl4 injection, and (PE-CCl4-PE): The rats were administered with PE pre, during, and after CCl4. The markers of oxidative stress ("OS": oxidant and antioxidants), inflammation [nuclear factor-κB, tumor necrosis factor-α, and interleukin-6], fibrosis [transforming growth factor-ß], and apoptosis [tumor suppressor gene (p53)] were evaluated. Additionally, liver functions, liver histology, and kidney functions were measured. Also, PE characterization was studied. The results showed that PE, in vitro, has a high antioxidant capacity because of the existence of phenolics, flavonoids, tannins, terpenoids, and minerals. Otherwise, the PE administration [groups (PE-CCl4) and (PE-CCl4-PE)] exhibited its prophylactic and therapeutic role versus the hepatotoxicity induced by CCl4 where PE treatment improved liver functions, liver histopathology, and renal functions by decreasing oxidative stress, inflammation, fibrosis, and apoptosis induced by CCl4. Our study elucidated that PE contains high amounts of phenolics, flavonoids, tannins, terpenoids, and ascorbic acid. So, PE exerted significant prophylactic and curative effects against hepatotoxicity induced by CCl4. These were done by enhancing the markers of antioxidants and drug-metabolizing enzymes with reductions in lipid peroxidation, inflammation, fibrosis, and apoptosis. PE administration for healthful rats for 12 weeks had no negative impacts. Consequently, PE is a promising agent for the prohibition and therapy of the toxicity caused by xenobiotics.

The antioxidant and anti-inflammatory effects of Carica Papaya Linn. seeds extract on CCl4-induced liver injury in male rats.

BACKGROUND: Oxidative stress (OS) and inflammation are the central pathogenic events in liver diseases. In this study, the protective and therapeutic role of Carica Papaya Linn. seeds extract (SE) was evaluated against the hepatotoxicity induced by carbon tetrachloride (CCl4) in rats. METHODS: The air-dried papaya seeds were powdered and extracted with distilled water. The phytochemical ingredients, minerals, and antioxidant potentials were studied. For determination of the biological role of SE against hepatotoxicity induced by CCl4, five groups of adult male Sprague-Dawley rats were prepared (8 rats per each): C: control; SE: rats were administered with SE alone; CCl4: rats were injected subcutaneously with CCl4; SE-CCl4 group: rats were administered with SE orally for 2 weeks before and 8 weeks during CCl4 injection; SE-CCl4-SE group: Rats were administered with SE and CCl4 as mentioned in SE-CCl4 group with a prolonged administration with SE for 4 weeks after the stopping of CCl4 injection. Then, the markers of OS [lipid peroxidation (LP) and antioxidant parameters; glutathione (GSH), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione peroxidase (GPx)], inflammation [nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-6], fibrosis [transforming growth factor (TGF)-ß], apoptosis [tumor suppressor gene (p53)], liver and kidney functions beside liver histopathology were determined. RESULTS: The phytochemical analyses revealed that SE contains different concentrations of phenolics, flavonoids, terpenoids, and minerals so it has potent antioxidant activities. Therefore, the treatment with SE pre, during, and/or after CCl4 administration attenuated the OS induced by CCl4 where the LP was reduced, but the antioxidants (GSH, SOD, GST, and GPx) were increased. Additionally, these treatments reduced the inflammation, fibrosis, and apoptosis induced by CCl4, since the levels of NF-κB, TNF-α, IL-6, TGF-ß, and p53 were declined. Accordingly, liver and kidney functions were improved. These results were confirmed by the histopathological results. CONCLUSIONS: SE has protective and treatment roles against hepatotoxicity caused by CCl4 administration through the reduction of OS, inflammation, fibrosis, and apoptosis induced by CCl4 and its metabolites in the liver tissues. Administration of SE for healthy rats for 12 weeks had no adverse effects. Thus, SE can be utilized in pharmacological tools as anti-hepatotoxicity.

The effect of leptin on maturation of the ovarian compartments of albino rats: an ultrastructural and histological study.

BACKGROUND: Leptin serves as a signal to the central nervous system with information on the critical amount of adipose tissue stores that is necessary for activation of the hypothalamic-pituitary-ovarian axis. OBJECTIVES: To document the histological and ultrastructural changes that occur in the ovarian follicles of immature albino rats treated with leptin when compared with controls. Furthermore, the endometrial histological and immunohistochemical, and vaginal cytological changes suggestive of ovulation were assessed. ANIMALS AND METHODS: The study was carried out on 50 immature female albino rats aged 22 days; 24 of them were injected with 5 microg leptin daily and 26 rats were taken as controls. Vaginal smears were taken daily, three animals were sacrificed every 2-4 days from each group, ovaries and uteri were dissected and specimens were prepared for electron microscopic, histological and/or immunohistochemical assessment. The research project was approved by The Histology Department Committee of Alexandria Medical School, which is licensed for animal care and use. RESULTS: Electron microscopic and histological examination confirmed the occurrence of maturational changes in various ovarian components from 26 days of age in leptin-treated rats, with ovulation occurring from the age of 30 days. The granulosa, theca and stroma cells showed signs of steroidogenesis, with increased mitosis within granulosa cells. The ooplasm showed an increased number of organelles, and annulate lamellae were demonstrated. The zona pellucida revealed microvilli, adhering junctions and gap junctions. Similarly, the endometrial histological and vaginal cytological maturational changes were detected in leptin-treated rats from 26 days of age. Furthermore, there was high expression of estrogen receptor-alpha in almost all columnar and stroma cells of the endometrium. However, the control rats ovulated around the normal age of maturation, i.e. 42 days. CONCLUSION: We documented ultrastructural, histological, immunohistochemical and cytological evidence that leptin accelerates the onset of puberty in female albino rats. The potential role of exogenous leptin, in cases of impaired reproductive function in humans, needs to be elucidated.