Protective effects of analogs of luteinizing hormone-releasing hormone against x-radiation-induced testicular damage in rats.

Abstract

Possible protective effects of the agonist [DTrp6]LH-RH (analog of luteinizing hormone-releasing hormone in which Gly-6 is replaced by D-tryptophan) and antagonist N-Ac-[D-Phe(pCl)1'2,D-Trp3,D-Arg6,D-Ala10]LH-RH against testicular damage caused by x-radiation were investigated in rats. Three months after being subjected to xirradiation of the testes with 415 or 622 rads, control rats showed marked reduction in the weights of the testes and elevated levels of LH and follicle-stimulating hormone (FSH), indicating tubular damage. Histological studies demonstrated that, in testes of rats given 415 rads, most seminiferous tubules had only Sertoli cells and no germinal cells, and, in the group given 622 rads, the depression of spermatogenesis was even more marked. Rats pretreated for 50 days with LH-RH antagonist (1000 ,ug/kg of body weight per day) showed a complete recovery of testicular weights and spermatogenesis 3 months after 415 rads and showed partial recovery after 622 rads, and LH and FSH levels returned to normal in both of these groups. Thus, pretreatment of rats with LH-RH antagonist, by reversibly inhibiting gonadal function, protected the germinal cells of the testes against damaging effects of x-rays. Three experiments were also carried out in which the rats were pretreated for 1-2 months with long-acting microcapsules of the agonist [D-Trp6]LH-RH, liberating 25 ,ug of the agonist per day. Some rats were then subjected to gonadal irradiation with 415 or 622 rads and allowed a recovery period of 2-4 months.In spite of pretreatment with [p-Trp6]LH-RH, testicular weights were significantly lower and LH or FSH levels were elevated in the irradiated groups as compared with nonirradiated controls. The recovery of spermatogenesis was incomplete, and there was a decrease in the number of germinal cells after 415 rads and especially after 622 rads. On the basis of testicular weights, histology, and gonadotropin levels, it could be concluded that the agonist [D-Trp6]LH-RH did not protect the rat testes exposed to 622 rads and, at most, only partially protected against 415 rads. These results suggest that pretreatment with LH-RH antagonists and possibly agonists, might decrease the testicular damage caused by radiation and accelerate the recovery of reproductive functions.

Protective effects of D-Trp6-luteinising hormone-releasing hormone microcapsules against cyclophosphamide-induced gonadotoxicity in female rats

“…This inhibitory effect is reversible, and gonadal recovery occurs after treatment with LH-RH agonists is discontinued. This approach has been suggested as a possible protective method against gonadal damage induced by chemotherapeutic drugs and radiation (Glode et al, 1982;Jarrel et al, 1987b;Karashima et al, 1988;Lewis et al, 1985;Schally et al, 1987;Schally, 1989).…”

Radyasyona Maruz Bırakılmış Sıçanlarda Spermatozoa Özellikleri ve Testislerde Yarattığı Hasar Üzerine Vitamin C’nin Koruyucu Rolü

“…The testes which generates male germ cells is known to be a radiosensitive organ in the body. The loss of testes weight following irradiation has been reported by several workers [21,22] . The loss in testes weight might be in part Radyasyon ve vitamini c uygulanan grupta dejenere olmuş ve hipospermatogenezisli (h) tübüllerin yanı sıra rejeneratif profil gösteren (r) ve normal spermatogenezis gözlenen seminifer tübüller (s) gösterilmiştir (c and f ).…”

Protective Effects of the Fermented Milk Kefir on X-Ray Irradiation-Induced Intestinal Damage in B6C3F1 Mice

“…In agreement with this finding, decreased testicular weights were reported after exposure of rat testes to X-ray irradiation. 6) Similarly, significant testicular weight losses were observed in mice after total-body irradiation 41) and focal pelvic gamma irradiation. 42) These findings are interpreted to indicate that irradiation of the testes induces germ cell apoptosis, particularly in actively dividing spermatogonia and preleptotene spermatocytes, thereby causing infertility in the irradiated testes.…”

“…Upon radiation, rapidly proliferating normal tissues, such as the intestinal mucosa and reproductive organs, are affected acutely and chronically. 6,31,32) The major function of the small intestine is the absorption of nutrients from ingested foods through the crypt-villus units, which are critically important for the maintenance of health. 8,9) However, functional cryptvillus units are susceptible to radiation because they contain rapidly dividing transit cells.…”

“…[3][4][5] GICs are caused by damage to ionizing radiation (X-rays, γ-rays)-sensitive tissues that contain rapidly regenerating cells, as exemplified by the gastrointestinal, reproductive and hematopoietic systems. [4][5][6] Above all, the small intestine is considered to be the most radiosensitive organ. 7) The absorptive epithelial mucous lining of the small intestine bears finger-like structures termed villus projections on its lumen.…”