l-Ascorbic acid partially protects two cycles of cisplatin chemotherapy-induced testis damage and oligo-astheno-teratospermia in a mouse model.
Cisplatin (cis-diaminedichloroplatinum-II) is a widely used antineoplastic agent in the treatment of a variety of cancers. The aim of the present study was to investigate the testicular toxicity of cisplatin in mice at human therapeutic dose-levels, and to investigate any protective effects of concomitantly administered l-ascorbic acid (i.p.; 10 mg/kg). Adult male BALB/C mice (13-15-week-old) were treated (i.p.) with two cycles of 5 days each of cisplatin with 17 days of recovery period between cycles, as follows: Group I (G-I) - water (N = 10); Group II (G-II) -L-ascorbic acid (N = 6); Group III (G-III) - 1mg/kg (N = 6); Group IV (G-IV) - 1 mg/kg + L-ascorbic acid (N = 6); Group V (G-V) - 2.5 mg/kg (N = 6); and Group VI (G-VI) - 2.5 mg/kg + L-ascorbic acid (N = 8). All animals were sacrificed on third day after the last treatment. The testis weight was decreased in a dose-dependent pattern (G-III - 44% and G-V - 54% against G-I), but l-ascorbic acid (10 mg/kg) recovered the lost weight in G-VI up to 32% against G-V (p<0.05). Seminiferous tubular pathology was indicated by vacuoles, epithelial gaps, epithelial sloughing, delayed spermiation, malorientation of spermatids, germ cell degeneration, phagocytosis of spermatids, multinucleated germ cell formation and atrophy. Structurally abnormal tubules (G-III - 33%; G-V - 100%) were induced, and protective effects were seen in G-IV (77%) and G-VI (25%; p<0.05). The tubular diameter was decreased in G-III-VI, but recovery was seen only in G-IV. The epithelial height was decreased in G-III, G-V and G-VI and the recovery was seen only in G-VI. The sperm count was decreased up to 53% and 71% against control in G-III and G-V, respectively, and recovery up to 47% and 61% was observed in G-IV and G-VI, respectively. The sperm motility was decreased up to 56% and 63% against control in G-III and G-V, respectively, and recovery was only marginal in G-IV and G-VI (p>0.05). Total sperm abnormalities were increased in G-III-V (274%, 156% and 232%, respectively, p<0.05) and l-ascorbic acid protected the effect in G-VI up to 156% (p<0.05). In conclusion, at human therapeutic dose-levels, cisplatin induces testicular damage and spermato-toxicity. l-Ascorbic acid only partially nullifies the gonadotoxic effects of cisplatin.
Narayana
K
K
Department of Anatomy, Faculty of Medicine, HSC, Kuwait University, P.O. Box no. 24923, Safat 13110, Kuwait. narayana68@yahoo.com
Verghese
Susan
S
Jacob
Saju S
SS
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001205:Ascorbic Acid / Q000494:pharmacology*; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009845:Oligospermia / Q000139:chemically induced*; D013076:Sperm Count; D013737:Testis / Q000187:drug effects* / Q000473:pathology
D000970:Antineoplastic Agents; D001205:Ascorbic Acid; D002945:Cisplatin