Abstract
Background:
A mancozeb, belonging to a pesticide, can induce testicular injury via free radical generation and antioxidant suppression. Pinus pinaster extract (Pycnogenol®) and L. carnitine have potent antioxidant properties.

Aim:
This study aimed to compare and evaluate the therapeutic roles of P. pinaster extract (Pycnogenol®) and L. carnitine in eliminating and/or reducing the testicular toxicity of mancozeb in male rats, emphasizing their combined antioxidant.

Methods:
Testicular toxicity was induced by oral administration of mancozeb (MCZ) at a dose of 313.6 mg/Kg for 4 weeks. Fifty male rats were allocated randomly into 5 groups, each group contained 10 rats. The first group (control group; C), second group (mancozeb group; MCZ) was orally administered 313.6 mg/Kg of mancozeb as a single dose/day for 4 weeks, third group (MCZ+PPE) received MCZ as the second group then administered P. pinaster extract (Pycnogenol®) at dose 40 mg/ Kg/day/ orally for 4 weeks, fourth group (MCZ+LC) was treated as the second group then administered L. carnitine at dose 200 mg/Kg/day/orally for 4 weeks. The fifth group (MCZ+PPE+LC) was treated as the second group and then received PPE and LC at the same doses mentioned in the third and fourth groups for 4 weeks.

Results:
Testicular follicle-stimulating hormone receptor (FSHr) and luteinizing hormone receptor (LHr) gene expression was significantly upregulated in rats that received PPE + LC+ MCZ compared with the experimental rats. The seminal fluid quality was significantly elevated while abnormal morphology significantly declined in the MCZ+PPE, MCZ+LC, and MCZ+PPE+LC groups compared with the MCZ group. The serum FSH, testosterone, LH, and antioxidant enzymes, superoxide dismutase, and glutathione peroxidase, increased significantly, whereas malondialdehyde decreased significantly in rats that received PPE+ LC+ MCZ compared with all experimental rats. In addition, based on testicular-histopathological investigations, the administration of both PPE and LC, alone or in combination, can improve testicular disarrangement due to mancozeb-induced testicular damage.

Conclusion:
The administration of P. pinaster extract and L. carnitine, individually or in combination, has antioxidant effects against mancozeb-induced toxicity via improvement of seminal quality, regeneration of testicular tissues, and upregulation of FSHr and LHr genes positively influence reproductive hormones. This study is the first to demonstrate that the P. pinaster extract plays a therapeutic role in testicular atrophy caused by the fungicide, mancozeb.

Key words: L. carnitine, Mancozeb, Pinus pinaster, Therapeutic, Testicular atrophy