الفهرس 
Introduction and Aim of the Work )Only 14 pages are availabe for public view
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Abstract
Cadmium is a widespread environmental pollutant that occurs primarily in the manufacture of batteries, electroplating, pigments, plastics and fertilizers. Acute and chronic toxicity of cadmium In both people and animals, has been linked to serious damage to several organs, notably the testes (Webb 1979).
Oxidative stress, inflammation and apoptosis are major factors responsible for cadmium-induced tissue damage (Gupta et al. 2004b). Naringenin is a flavanone glycoside widely found in citrus and grape fruits, soybean, cherry, cocoa, tomato and grapefruit juices (Rong et al. 2017). NAR has been scientifically proven to have beneficial effects on a variety of pathological disorders, including cardiovascular disease, hyperlipidemia, atherosclerosis, diabetes, neuropathy, liver dysfunction, nephropathy, and cancer (Chen et al., 2018). Likewise, another natural drug, vanillin, protects against cadmium-induced tissue damage in many tissues mediated by antioxidant, anti-inflammatory, and anti-apoptotic mechanisms (Bezerra et al., 2016). Vanillin is one of the most commonly used flavor compounds found naturally in vanilla and potato vegetables (Zamzuri and Abd-Aziz 2013). This study was conducted to investigate the effects of naringenin and vanillin on Cd-induced testicular changes in rats and to determine if the combination of both drugs could provide additional beneficial effects when compared to monotherapy. The rats were randomly divided into five groups. The first group (n = 6) received a single intraperitoneal dose. Saline (cadmium carrier) was injected and served as a control. Testicular injury was induced in 2nd, 3rd, 4th and 5th groups of rats in
(n = 6 each) with a single i.p. Cadmium chloride injection at a dose of 2 mg/kg (Gupta et al. 2004b). Animals in the third and fourth groups received naringenin (50 mg/kg/day, oral) and vanillin (150 mg/kg/day, oral) intraperitoneally for 8 and 1 days, respectively. CdCl2 injection was performed on day 6. A fifth group of animals received NGN + VLN once intraperitoneally for 8 consecutive days. On day 6, CdCl2 was injected. At the end of the experiment, the mice were sacrificed by beheading the cervix 48 hours after CdCl2 administration. The testicles are carefully excised and weighed. The clear serum was then isolated and stored at 80°C until various parameters were measured. Before analysis, testicular tissue was collected in PBS (phosphate buffered saline) (0.05 M, pH 7.4) and homogenized to obtain a homogenate, and then the supernatant was separated and analyzed in various ways. To achieve this goal, the following Cd-induced rats were performed in the presence and absence of study drug therapy:
1. Testicular weight assessment. 2. Testicular function is assessed by measuring serum testosterone levels. 3. A study of the effect on oxidative stress status by measuring the content of malondialdehyde (MDA), total nitrite and total antioxidant capacity (TAC) in testicular tissue. 4. Measurement of the level of tumor necrosis factor (TNFα) in serum to study the effect on the inflammatory state. 5. Measurement of signal-regulated testis expression of phosphorylated extracellular protein protein kinases 1 and 2 (pERK1/2). 6. Measurement of testicular phosphorylation signal transducer and transcriptional protein expression activator 3 (pSTAT3). 7. Histopathological examination of testicular tissue.
8. Assessment of apoptosis by immunohistochemical evaluation of Bax and caspase 3 in testicular tissue. In this study, treatment with naringenin and vanillin improved antioxidant properties and reduced oxidative stress, as shown by an increase in antioxidant status (TAC) and a decrease in MDA and NOx levels. Treatment with naringenin and vanillin can significantly increase low serum testosterone levels as well as decrease elevated tumor marker (TNFα) levels. Interestingly, treatment with naringenin and vanillin suppressed the expression of pERK1/2 and pSTAT3 proteins in testis. Moreover, naringenin and vanillin were able to ameliorate apoptosis and histological changes, which resulted in testicular tissue in mice addicted to CD.