A stereological study of the effects of antidepressants on postmenopausal rat kidney.

Many factors can cause depression including genes (DNA), brain chemistry or stress. Antidepressant drugs affect the brain, heart, liver and kidney. We investigated the effects of the antidepressant drugs, amitriptyline (AMI) and paroxetine (PARO) on kidney. We used 24 adult female rats that were ovariectomized bilaterally 7 days before the experiment. The ovariectomized (OVX) animals and healthy control rats were divided into four equal groups for 4 weeks: control group, OVX control group (sham), AMI group and PARO group. Following the experimental period, the Cavalieri method was applied to sections of the kidney. PARO produced adverse effects on distal and proximal tubule volume, but AMI had no effect on the volume of distal and proximal tubules. Both PARO and AMI decreased the volume of Bowman spaces. PARO also damaged the kidney tubules and cells.

Effect of vitamin C on collagen structure of cardinal and uterosacral ligaments during pregnancy.

OBJECTIVE: This study aimed to investigate changes in collagen structure in the cardinal and uterosacral ligaments of rats that were administered vitamin C during pregnancy. STUDY DESIGN: Eighteen female rats were divided into three groups: six pregnant rats administered 1.25mg/ml/day of vitamin C during pregnancy (Group A); six non-pregnant rats that were not administered vitamin C (Group B); and six pregnant rats that were not administered vitamin C during pregnancy (Group C). Fifteen days after delivery, the uteruses of all rats were removed. The intensity of staining (mild, moderate or severe) and the extent of positive staining areas (%) of type I and type III collagen H scores for types I and III collagen, and intensity of elastin fibres in the cardinal and uterosacral ligaments were investigated immunohistochemically. Differences between groups were analysed using Kruskal-Wallis and independent samples tests. RESULTS: The intensity and extent of type I and type III collagen, the H scores for type I and type III collagen, and the ratio of type III collagen H score: type I collagen H score differed significantly between groups. Pregnant rats administered vitamin C (Group A) had significantly higher values compared with non-pregnant rats (Group B): intensity of type I collagen (p=0.001), extent of type I collagen (p≤0.001), H score for type I collagen (p≤0.001), intensity for type III collagen (p=0.002), extent of type IV collagen (p=0.007), H score for type III collagen (p=0.017), type III collagen H score: type I collagen H score (p=0.039) and intensity of elastin fibres (p=0.097). A significant difference in the ratio of type III collagen H score: type I collagen H score was found between pregnant rats administered vitamin C (Group A) and pregnant rats not administered vitamin C (Group C) (p=0.002). CONCLUSIONS: The administration of vitamin C to rats during pregnancy had a favourable impact on collagen structure in the cardinal and uterosacral ligaments, suggesting that vitamin C supplementation during pregnancy may help to prevent pelvic organ prolapse and stress urinary incontinence.

The effect of FAAH, MAGL, and Dual FAAH/MAGL inhibition on inflammatory and colorectal distension-induced visceral pain models in Rodents.

BACKGROUND: Recent studies showed that the pharmacological inhibition of endocannabinoid degrading enzymes such as fatty acid amide hydrolase (FAAH) and monoacyl glycerol lipase (MAGL) elicit promising analgesic effects in a variety of nociceptive models without serious side effects. However, the full spectrum of activities is not observed upon inhibition of either FAAH or MAGL enzymes alone and thus dual FAAH and MAGL inhibitors have been described. Visceral pain is strongly associated with inflammation and distension of the gut. Thus, we explored the comparable effects of FAAH, MAGL, and dual FAAH/MAGL inhibitors on inflammatory and mechanically evoked visceral pain models. METHODS: Visceral inflammatory and distension-induced pain were assessed with the 0.6% acetic acid writhing test in mice and colorectal distension (CRD) test in rats, respectively. The selective FAAH inhibitor PF 3845, MAGL inhibitor JZL 184, dual inhibitor JZL 195, and the cannabis analog CP 55,940 were given systemically 30 min prior to nociceptive testing. KEY RESULTS: PF 3845 (5, 10, and 20 mg/kg), JZL 184 (5, 10, and 20 mg/kg), and JZL 195 (5, 10, and 20 mg/kg) elicit dose-dependent antinociceptive in the acetic acid writhing test. In the CRD model, while JZL 195 (5, 10, or 20 mg/kg) and PF3845 (10, 20, and 40 mg/kg) produced dose-dependent antinociceptive effects comparable to those of CP 55,940 (0.1, 0.3, or 1 mg/kg), JZL 184 (10, 20, and 40 mg/kg) alone did not alter the visceromotor response (VMR). CONCLUSIONS & INFERENCES: The selective FAAH inhibitor and dual FAAH/MAGL inhibitors were effective in both inflammatory and mechanically evoked visceral pain, while the MAGL inhibitor elicited an analgesic effect in inflammatory, but not in distension-induced, visceral pain.

The combination of agomelatine and ritanserin exerts a synergistic interaction in passive avoidance task.

Agomelatine is a potent agonist at melatonergic 1 and 2 (MT1 and MT2) receptors and an antagonist at serotonin-2C (5HT-2C) receptors. It was suggested that psychotropic effects of agomelatine is associated with its melatonergic and serotonergic effects. In this study, we aimed to evaluate the effects of agomelatine alone or in combination with ritanserin (5HT-2A/2C antagonist) on memory and learning. Male Balb-C mice (25-30 g) were used, and all drugs and saline were administrated by intraperitoneal (i.p.) route 30 min prior to evaluating retention time. Whilst agomelatine was administered at the doses of 1, 10 and 30 mg/kg, ritanserin was administered at the doses of 0.1, 1 and 10 mg/kg. To evaluate memory function, passive avoidance test was used. On the first day, acquisition time and on the second day (after 24h), retention time of mice were recorded. To evaluate the synergistic activity, only the least doses of agomelatine and ritanserine were used, that is, 1 and 0.1 mg/kg, respectively. Scopolamine (1 mg/kg) was used as a reference drug, so it was combined with drug groups. Our results show that 5HT-2A/2C receptor antagonist ritanserin (1 and 4 mg/kg, i.p.) and agomelatine (10 and 30 mg/kg, i.p.) improve memory deficit induced by scopolamine, whilst a synergistic interaction is observed between ritanserin and agomelatine (0.1 mg/kg and 1 mg/kg, i.p., respectively) when they were administered at their ineffective doses. According to our findings, we concluded that agomelatine improves memory deficit and thus improves the effect of agomelatine arises from its 5HT-2C receptor antagonist activity.

The effect of zoledronic acid on growth plates and high turnover bones.

OBJECTIVES: Bisphosphonates have preventive effect on bone resorption caused by osteoclasts.We aimed to investigate the histopathological effects of zoledronic acid (ZA) on the jaw and long bones and growth plates of rats. METHODS: Thirty-six 12 week-old female Sprague-Dawley rats were divided into the control (C, n=18) and ZA groups (Z, n=18). Z group animals were administered 0.1 mg/kg saline-diluted ZA intraperitoneally three times per week for 8 weeks. C group animals were administered the same amount of saline simultaneously. At the end of 11th week, half the subjects from either the control group (C1) and ZA group (Z1) were sacrificed. At the end of 14th week, the remaining half from both groups were also sacrificed (C2 and Z2). In all animals, no dental procedures were performed; the posterior and anterior mandible and the knee joint including distal femur and proximal tibia were histopathologically investigated. RESULTS: Histological examination revealed that inflammation and necrosis were limited to the posterior mandible of the Z1 and Z2 groups, while the anterior mandible and knee joint including distal femur and proximal tibia remained unaffected however the development of the growth plate of the proximal tibia was found to be arrested in animals of the Z1 and Z2groups. CONCLUSION: Due to it is inhibitory effect over growth plate and inflammatory and necrotic effect over high turnover bones, zoledronic acid should be administered cautiously, especially in pediatric patients who are still in their growth and development stages (Fig. 6, Ref. 34).