Isotretinoin's action against cisplatin-induced ototoxicity in rats.

Current data do not support the routine use of any agent to prevent cisplatin ototoxicity. Although there are various diseases in which derivatives of vitamin A are used due to their antioxidant effects, there is no study for prevention from ototoxicity. In this study, the protective effect of isotretinoin was investigated on cisplatin ototoxicity in rats. 21 Wistar Albino rats were divided randomly into 3 groups. Group I: cisplatin, Group II: cisplatin + isotretinoin and Group III was the control group. Hearing assessment of all rats was done with ABR and DPOAE tests before and after the procedure. After the procedure, cochleas were resected and transmission electron microscopic examination was performed. Our DPOAE and ABR findings showed that isotretinoin has protective effects on cisplatin ototoxicity. According to transmission electron microscopic findings, isotretinoin has protective effects on cell integrity. We think that new experimental and clinical studies to be carried out in this regard may give us a new option on prevention of cochlea from ototoxicity.

The comparison of the degree of apoptosis in ovaries and fallopian tubes between two different surgical interventions for tubal ligation: A rat model.

OBJECTIVE: To compare the degree of apoptosis in ovaries and tubal epithelium observed secondary to tubal ligation either by Pomeroy's method or bipolar electrocauterization in a rat model. MATERIAL AND METHODS: A total of 24 female Sprague-Dawley rats were randomly assigned into 3 study groups: control (n=8), Pomeroy (n=8), and the electrocauterization group (n=8). Apoptotic cells were detected on the primary, secondary, tertiary follicles of the ovaries, and on the tubal epithelium using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling. The apoptotic index was calculated for each group by the percentage of the stained cells. RESULTS: The apoptotic index of tubal epithelium was significantly higher in the bipolar electrocauterization group compared with the control and Pomeroy groups (3.1±0.8 vs. 1.4±1.0, p=0.018 and 2.0±1.2, p=0.03, respectively) whereas there was no significant difference between Pomeroy's method and the control group. The apoptotic index of primary follicles was higher in the bipolar electrocauterization group compared with the control and Pomeroy's method groups (3.4±0.5 vs. 1.2±0.4, p<0.001 and 1.8±0.8, p=0.005, respectively), but there was no significant difference between Pomeroy's method and the control group. The apoptotic index of secondary and tertiary follicles was similar for each group. CONCLUSION: Pomeroy's technique, as a permanent contraception method, is associated with lower apoptotic index on ovary and fallopian tube when compared with bipolar electrocauterization.

The Impact of a Long-Acting Oral Sphingosine-1-Phosphate Analogue on Ovarian Aging in a Rat Model.

In animal studies, intravenous continuous infusion or peritoneal injection of sphingosine-1-phosphate (S1P) has been shown to decrease chemotherapy- and radiotherapy-induced apoptosis on primordial follicles. Although a long-acting oral form of an S1P analogue (FTY720, fingolimod) has been recently developed and utilized in women with multiple sclerosis, there are no data exploring its ability to avoid spontaneous follicle apoptosis. Thirty 10-month-old female rats were randomly assigned to 3 groups to investigate whether fingolimod would be able to decrease the spontaneous ovarian follicle apoptosis ratio. An oral analogue form of S1P was administered for 60 days at a dose of 0.1 mg/kg (n = 10) or dose of 1 mg/kg (n = 10) per day. The control group (n = 10) received physiological serum via an orogastric feeding tube. The main outcome measures were anti-Müllerian hormone (AMH) level and nonapoptotic follicle ratio. While low-dose S1P group had comparable AMH levels to high-dose S1P group and controls, high-dose S1P group had higher mean levels of AMH, reaching marginal significance with controls (5.72 ± 0.61 vs 4.81 ± 0.85 ng/mL, P = .050). For the nonapoptotic primordial follicle ratio, both low-dose S1P group (67.0% ± 16.4% vs 29.9% ± 19.5%, P < .001) and high-dose S1P group (51.1% ± 11.5% vs 29.9% ± 19.5%, P = .023) had superior rates when compared with controls. Interestingly, low-dose S1P groups also had a statistically higher nonapoptotic primordial follicle ratio than high-dose S1P group ( P = .047). Our findings suggest that a long-acting oral analogue of S1P might decrease spontaneous follicular apoptosis based on the nonapoptotic primordial follicle ratio and AMH levels when compared with placebo.