Melatonin supplementation in rat ameliorates ovariectomy-induced oxidative stress.

OBJECTIVE: The present study aims to determine the potential of melatonin supplementation in ameliorating tissue oxidative stress, elevated serum corticosterone and hepatic and renal dysfunction. MATERIALS AND METHODS: Adult Wistar rats, either ovariectomized or sham-operated, served as experimental or control groups, respectively. Rats received either melatonin, estrogen, progesterone or a combination of melatonin and estrogen for a period of 15 days. Tissue oxidative stress, serum markers of hepatic and renal dysfunction and serum corticosterone level formed the parameters of assay in all groups at the end of the treatment schedule. RESULTS: Ovariectomized rats showed significant increases in levels of tissue lipid peroxidation, serum levels of glutamic pyruvic transaminase, glutamic oxaloacetic transaminase, alkaline phosphatase, acid phosphatase and corticosterone and significant decrement in enzymatic and non-enzymatic antioxidant status. All parameters showed maximal reversal to control levels on supplementation with high-dose melatonin or estrogen + melatonin treatment. CONCLUSION: Melatonin supplementation proved better than estrogen replacement therapy, with the higher dose being more effective in preventing ovariectomy-induced increases in oxidative stress and serum levels of marker parameters of hepatic and renal dysfunction and corticosterone titer. Overall, melatonin supplementation therapy qualifies as a more potent and safe alternative to estrogen replacement therapy in alleviating postmenopausal increases in oxidative stress and hepatic and renal dysfunction.

Excess choline availability: a transient effect on spermatogenesis in the rat.

The reproductive effects of choline (trimethyl-beta-hydroxyethylammonium) are unknown. Excess dietary intake of choline may occur in humans. Adult male rats were administered i.p. aqueous choline chloride (25 mg/rat, daily for 12 or 24 days). Administration of excess choline for 12 days did not significantly alter spermatogenesis. Administration for 24 days depleted pachytene spermatocytes until posttreatment day 5, while slight proliferation of spermatogonia was noted from day 5 onwards. By day 12, the tubules showed almost normal cellular associations. It is suggested that perhaps a prolonged administration of excess choline may prove to be toxic to male reproduction.

Histomorphological changes in lung of rats following exposure to wood smoke.

Rats were exposed to repeated, intermittent exposure to smoke generated from combustion of 1g wood/15 min, total period for 75 min daily under dynamic exposure conditions, over a period of 15, 30 and 45 days. First 15 days exposure caused mild bronchiolitis, hyperplasia and hypertrophy of bronchiolar epithelial lining cells, some necrosed lining cells desquamated into lumens, congestion of parenchymatous blood vessels, oedema, hyperplasia of lymphoid follicles, peribronchiolar and perivascular infiltration of polymorphonuclear cells, and mild emphysema. These lesions progressed further during 30 and 45 days of exposure, though emphysematous changes remain constant. By 30 days and 45 days, hyperplastic and hypertrophic changes of bronchioles become quite marked, with mononuclear cells infiltration and alveolar septa thickening. Hematological studies show marginal alterations in hemoglobin levels, ESR, PCV and TLCS during 15 days, where as significant changes in eosinophil were observed during 30 and 45 days, and ESR during 45 days only. The results indicate progressive pathomorphological pulmonary lesions with subsequent exposure to wood smoke in controlled conditions.

Stage specific effect during one seminiferous epithelial cycle following ethylene glycol monomethyl ether exposure in rats.

Stage specific effect of single oral dose (500 mg/kg body wt) of ethylene glycol monomethyl ether (EGME) was characterised during one cycle of seminiferous epithelium in rats. Maximum peritubular membrane damage and germinal epithelial distortion were observed at stages IX-XII. Cell death occurred during conversion of zygotene to pachytene spermatocytes (stage XIII) and between dividing spermatocytes and step I spermatids (stage late XIII-XIV). Profound effect was noted during first meiotic division than during second meiotic division. Presence of multinucleated secondary spermatocytes indicated cytokinesis arrest. The spermatogenesis was delayed and consequently frequency of tubules at stages I-VIII was reduced by day 10. Many of the tubules were devoid of round spermatids on day 12. Possibly, EGME (or it's metabolite) distorted the barrier system at stages IX-XIV and damaged the cells mostly at stages XII-early XIV.

Testicular toxicity of methylmercury: analysis of cellular distribution pattern at different stages of the seminiferous epithelium.

Stage-specific distribution of methylmercury (MM) and spermatogenic changes were analyzed in rats administered 5 or 10 micrograms MM/kg, ip, daily for 15, 30, 60, and 90 days. MM deposition, as grain number/cm2 was noted in basal portions at later stages on day 15, which increased gradually by day 90. MM deposition was in the order of stages IV, VII, XIV, IX, being higher in adluminal portions on days 30 and 60. MM-enriched cytoplasmic masses leaked out through disintegrated tubular membrane on days 60 and 90. Epithelial damage, at stages late XIV through IV, V through VI, VII through VIII, XIII through mid-XIV, and IX through XII, accorded with the gradual deposition of MM. As profound cell death occurred between zygotenes to pachytenes and dividing spermatocytes to step 1 spermatids, the spermatids were conspicuously decreased at later times. It is possible that MM distorts the barrier system at stages IX through XII, gets distributed within the tubule, and hence may pose a direct or Sertoli cell mediated effect at stages XII through early XIV in a dose-duration-MM burden related manner.

Distribution of mercury and evaluation of testicular steroidogenesis in mercuric chloride and methylmercury administered rats.

Intraperitoneal administration of methylmercury chloride (MMC) and mercuric chloride (MC) to male rats in doses of 5, 10 micrograms MMC/kg or 50, 100 micrograms MC/kg for 90 days induced cellular disintegration of Leydig cells which was conspicuous on day 30 and onwards in the exposed groups. Progressive degeneration of Leydig cells and decrease in their nuclear diameter and population were associated with gradual increase in deposition of mercury. Gradual diminution of 3 beta-hydroxy-delta 5-steroid dehydrogenase activity in Leydig cells after MMC or MC treatment was correlated with different structural deformations of the cells over 90 days. Moreover, a significant decrease in serum testosterone levels by day 90 confirmed steroidogenic impairment after MMC or MC treatment.

Methylmercury induced biochemical and histochemical alterations in rat testis.

The methylmercurry chloride (MMC) administered at doses of 5 and 10 micrograms/kg over a period of 90 days to male rats caused enzymatic impairments in testicular tissue. The study at intervals of 15, 30, 60 and 90 days showed gradual diminution of testicular weight and gradual decrements in testicular protein and inhibition in testicular succinic dehydrogenase activity. Histochemical and biochemical studies revealed that testicular acid phosphatase activity was also inhibited at both the doses of MMC treatment. The inhibition of enzyme activity in testicular tissues after MMC treatment caused the impairment of both spermatogenesis and steroidogenesis in rats.

Methylmercury- and mercuric-chloride-induced alterations in rat epididymal sperm.

Four-week-old male albino rats weighing 70 +/- 5 g were treated intraperitoneally daily with 0, 5 and 10 micrograms methylmercuric chloride (MMC)/kg or 0, 50 and 100 micrograms mercuric chloride (MC)/kg body weight, respectively, over a period of 90 days. Studies were carried out a intermittent intervals, i.e. on days 0, 15, 30, 60 and 90 of the experiment. Gradual decrements in body and epididymal weights were observed from day 30 onwards in both the MMC- and MC-treated groups. Morphological deformations of epididymal epithelium were noted from day 30 onwards in the mercurial-treated groups. MMC treatment caused severe degeneration of the epididymal epithelium on days 60 and 90 in comparison to MC treatment. Total sperm count was significantly less in the MC-treated groups, while motile sperm count was affected most in the MMC-administered groups. The frequency of sperm abnormality increased consistently at both doses of mercurial treatment over a period of 90 days. Maximum sperm abnormality among the treated groups was noted in the groups given 10 micrograms MMC/kg. The observations revealed that MMC and MC have variable potency to alter epididymal structure and the sperm.

Histomorphometric and biochemical changes in the testicular tissues of rats treated with mercuric chloride.

Gradual alterations of testicular tissues were noted in rats treated with mercuric chloride at dosages of 0.05 mg/kg and 0.10 mg/kg body weight (i.p.) over a period of 90 days. Significant reduction in body and testicular weights were observed throughout the experimental period in treated animals. Consequently, testicular protein, DNA and RNA also exhibited a similar type of diminution in the same groups. Moreover, high cholesterol and low ascorbic acid concentrations were found in testis at both doses. Testicular degeneration and spermatogenic arrest were more pronounced in the high dose group over a period of 90 days.

Inhibition of 3 beta-hydroxy-delta 5-steroid dehydrogenase in rat testicular tissue by mercuric chloride.

Histochemical investigations of 3 beta-hydroxy-delta 5-steroid dehydrogenase (delta 5-3 beta OHD) activity in the testicular tissue of rats administered mercuric chloride (HgCl2) at dosages of 0.05 mg/kg and 0.1 mg/kg (i.p.) daily for 90 days reveal a graded inhibition of delta 5-3 beta OHD activity which was positively related to dosage and to the duration of treatment with this compound. This phenomenon may be mainly responsible for the inhibition of spermatogenesis, observed as a toxic manifestation of mercury compounds.