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Abstract Obesity is a major risk factor for heart disease. Persistent exposure to excess lipids in the circulation can harm the heart by accumulating hazardous metabolic byproducts such reactive oxygen species (ROS) and ceramides, which can cause myocyte malfunction and death by activating particular signaling pathways. In general, people employ a variety of strategies to avoid the adverse effects and/or failure of standard weight-loss medications, such as meal replacements, exercise, and herbs. Herbs are one of the most popular weight- loss alternative medicines in the world. The bulk of these herbs are utilized as a raw plant, and herbs have been used to cure obesity all over the world in recent years. Efficacy and safety of medicinal plants in the treatment of obesity, dyslipidemia, and diabetes mellitus have been studied extensively. Our study aimed to evaluate the possible effects of celery seed oil against obesogenic diet induced lipotoxicity of heart in rats. The study was conducted on 40 male Wistar rats weighing from (150-250 grams), Obesity was induced in the animals by feeding a high fat diet for 12 weeks. The rats were divided into two groups: group I (Control group): Consists of 8 healthy male rats that were fed a normal diet. group II (obese group): Consists of 32 obese rats that were subdivided into four subgroups (8 rats each): group IIA: Untreated obese rats. Group IIB: Obese rats that were orally treated with orlistat drug in a dose of (30 mg/kg b. wt. / day) for four weeks. group IIC: Obese rats that were orally treated with celery seed oil in a dose of (300 mg/kg b. wt. /day) for four weeks. group IID: Obese rats that were orally treated with celery seed oil (300 mg/kg b. wt. /day) and orlistat (30 mg/kg b. wt. / day) for four weeks. At the end of treatment period, all rats were scarified, and then blood samples and heart tissues of the rats were collected for biochemical analysis to detect the progression of obesity and CVD. Blood samples were used for the determination of: Lipid profile, fasting glucose, Insulin level, Calculation of insulin resistance index using HOMA- IR, Malondialdehyde level, Ferric reducing antioxidant power and Nitric oxide end products (NOx). Heart tissues were used for determination of: Inducible nitric oxide synthase (iNOS), Peroxisome proliferator –activating receptor-α (PPARα), Ceramide, Triglycerides (TGs), Free fatty acid (FFA), Ferric reducing antioxidant power and Nitric oxide end products (NOx). The current results confirmed the ameliorative role of orlistat and celery seed oil treatment alone or in combination of celery seed oil with orlistat in CVD, the results showed a marked lowering of glucose homeostasis parameters, lipid profile, cardiac contents of TG, FFA, NO and ceramide. In addition, the present study indicated a down regulation in the cardiac expression of iNOS while an up regulation in the PPARα expression. from the above-mentioned discussion, we can conclude that: 1. Celery seed oil has a powerful glucose and lipid-lowering effect that plays an important role in the protection against obesity. Summary & Conclusion 71 2. Celery seed oil have ameliorative effect against obesogenic diet induced lipotoxic heart disease, through multiple interrelated mechanisms including, boosting the antioxidant status, suppressing the TG and FFA accumulation in cardiac tissues. 3. The used dose of celery seed oil produces anti-lipotoxic effects equivalent to orlistat, while combined group (orlistat with celery seed oil) showed the best effect. 4. Celery seed oil could be used for protection against obesity alone or used as adjuvant with orlistat drugs to enhance their pharmacological effect against lipotoxic heart disease. |