THE CURATIVE PROSPECTIVE ROLE OF "CLEOME DROSERIFOLIA" EXTRACT AND STEM CELLS AGAINST TOXICITY OF CYHALOTHRIN ON MALE ALBINO RATS

Abstract

Infertility and reproductive abnormalities caused by pyrethroid insecticides have been observed in human and many animals, such as inhibition of spermatogenesis, alteration of germinal cell DNA and seminiferous epithelium and low quality of sperms. The present study aimed to investigate possible protective and therapeutic role of Cleome droserifolia extract (CDE) and mesenchymal stem cells (MSCs), separately in the restoration of fertility and reproductive functions on testicular dysfunctions induced by ʎ-cyhalothrin (LCT) in male rats. Seventy adult male albino rats were divided into seven groups: group I: served as control, rats received orally olive oil+ distilled water, parallel to the drug treated groups; group II: received LCT only (6.23 mg/kg b.w., i.p.) dissolved in olive oil three times a week for two weeks; group III: received CDE only (100 mg/kg b.w., p.o.) dissolved in distilled water daily for eight weeks; group IV: rats treated with CDE (p.o.) as a protective agent daily for eight weeks and were given LCT (i.p.) on the 7th week three times a week for two weeks; group V: exposed to LCT (i.p.) three times a week on the 1st and 2nd weeks, then treated with the CDE daily for 8 weeks; group VI: rats injected (i.v.) with a single dose of MSCs (1x106 cells/ml PBS), then received dose of LCT (i.p.) three times a week for two weeks, and left until the 8th week and group VII: rats received dose of LCT (i.p.) three times a week on the 1st and 2nd weeks, then injected (i.v.) with a single dose of MSCs and left for 8 weeks. Results showed that, LCT caused significant reduction in the body and testis weight, and markedly impaired sperm quality (count, viability, motility and abnormality). A biochemical, LCT elicited significant declines in serum testosterone, total proteins and albumin, high density lipoprotein (HDL), whereas, serum follicle stimulating hormone (FSH) and luteinizing hormone (LH), total cholesterol, triglycerides (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) levels were significantly increased. Furthermore, LCT brought about significant disturbance in cytokines; tumor necrosis factor (TNF-α), interleukin-10 (IL-10) and interleukin-12 (IL-12) levels. Testicular glutathione (GSH) content and superoxide dismutase (SOD) activity reduced significantly, while, testicular malondialdehyde (MDA) level was significantly elevated after LCT administration as compared to the control group. Histological and ultrastructural changes were also in accord with the above aberrations, which showed atrophied seminiferous tubules with disruption of the boundary tissue, deformed spermatogenic cells, widened intertubular spaces, congested blood vessels and disappearance of almost all spermatozoa. Ultrastructural observations revealed thickening of the boundary tissue, disorganization of germ cells with distorted nuclei, dilated smooth endoplasmic reticulae and devastated mitochondria. Sertoli cells showed degenerative changes in the form of cytoplasmic vacuolization, increase of the lysosome numbers. Compared to LCT-treated animals, LCT+CDE-protective group markedly restored the alteration of body and testis weights, sperm indices, sexual hormones, proteins and lipids profile, cytokines, antioxidant and oxidative stress parameters. Moreover, it protects testicular tissues and cell structures. However, LCT+CDE-therapeutic group was found to be less effective in restoring biochemical, histological and ultrastructural alterations. LCT+MSCs-therapeutic group showed significantly improved the activity of all biochemical parameters and significant preservation in histological and ultrastructural configuration of the testis rather than LCT+MSCs-protective group which showed minimal protection against LCT. From the present data it can be concluded that protection by Cleome droserifolia extract (CDE) and therapy with mesenchymal stem cells (MSCs) were more effective than therapy and protection by CDE and MSCs, respectively, in ameliorating ʎ-cyhalothrin (LCT)-induced testicular damage and thus for improvement of testicular function and structure as well as male fertility. Key Words: Cleome droserifolia, Mesenchymal stem cells, ʎ-cyhalothrin, Reproductive functions, Testis, Rat.