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Showing papers by "Chandana Haldar published in 2014"


Journal ArticleDOI
TL;DR: It is suggested that melatonin improved defence against Dex‐induced testicular oxidative stress and prevented germ cell apoptosis, suggesting a novel combination therapeutic approach for management of male reproductive health.
Abstract: This study investigated the protective effect of melatonin on dexamethasone (Dex), an extensively used anti-inflammatory and immunosuppressive synthetic glucocorticoid, induced testicular oxidative stress and germ cell apoptosis in golden hamster. Hamsters were randomly divided into four groups (n = 7): group I - control; group II - melatonin treated (10 mg kg(-1) day(-1) ); group III - Dex treated (7 mg kg(-1) day(-1) ) and group IV - combination of Dex and melatonin. All the injections were administered intraperitoneally for seven consecutive days. The histopathological changes, specific biochemical markers, including antioxidative enzymes, plasma melatonin level and the markers for germ cell apoptosis were evaluated. Dex administration decreased antioxidant enzyme activities (SOD, CAT, GSH-PX ), plasma melatonin level and melatonin receptor (MT1) expression with a concomitant increase in lipid peroxidation (TBARS) and altered testicular histopathology which might culminate into increased germ cell apoptosis as evident from increased Bax/Bcl-2 ratio and caspase-3 expression. However, melatonin pre-treatment enhanced enzyme activities for SOD, CAT, GSH-PX with a simultaneous decrease in Bax/Bcl-2 ratio and caspase-3 expression. Our findings clearly suggest that melatonin improved defence against Dex-induced testicular oxidative stress and prevented germ cell apoptosis, suggesting a novel combination therapeutic approach for management of male reproductive health.

45 citations


Journal ArticleDOI
TL;DR: It is suggested that photoperiod via regulating circulatory and local melatonin level as well as MT1R expression in testes fine tunes the steroidogenesis and thereby, the reproductive status of male golden hamster.
Abstract: Photoperiodic modulation of melatonin membrane receptor (MT1R) expression in testis has never been reported for any seasonal breeder. Thus, the aim of the present study was to investigate the expression dynamics of MT1R in testis and its interaction with testicular steroidogenesis in a long-day breeder, Mesocricetus auratus . Hamsters were exposed to different photoperiodic conditions i.e. critical- (CP; 12.5L:11.5D); short-day- (SD; 8L:16D) and long-day- (LD; 16L:8D) for 10 weeks wherein testicular steroidogenesis, local melatonin synthesis and the expression of MT1R were analyzed. SD induced melatonin suppressed testicular steroidogenesis as evident from regressed testicular histoarchitecture, decreased expression of AR, StAR, LH-R, P 450 SCC and enzyme activities of 3β- and 17β-HSD. Differential photoperiodic regulation of MT1R expression in testis suggests its involvement in photoperiodic signal transduction for seasonal adjustment of reproduction. Increased S-NAT (Serotonin N-acetyl transferase) activity and local testicular melatonin under SD condition suggest an inhibitory effect of the local melatonergic system on testicular steroidogenesis. Completely opposite responses were recorded for all the parameters analyzed when hamsters were exposed to CP or LD conditions. In conclusion, we may suggest that photoperiod via regulating circulatory and local melatonin level as well as MT1R expression in testes fine tunes the steroidogenesis and thereby, the reproductive status of male golden hamster.

30 citations


Journal ArticleDOI
26 Sep 2014-PLOS ONE
TL;DR: Induction of mitochondrial apoptosis, ER stress and autophagy dysregulation provide a new insight into the mechanism of ATR immunotoxicity.
Abstract: Exposure to the herbicide Atrazine (ATR) can cause immunotoxicity, apart from other adverse consequences for animal and human health. We aimed at elucidating the apoptotic mechanisms involved in immunotoxicity of ATR and their attenuation by Melatonin (MEL). Young Swiss mice were divided into control, ATR and MEL+ATR groups based on daily (x14) intraperitoneal administration of the vehicle (normal saline), ATR (100 mg/kg body weight) and MEL (20 mg/kg body weight) with ATR. Isolated splenocytes were processed for detection of apoptosis by Annexin V-FITC and TUNEL assays, and endoplasmic reticulum (ER) stress by immunostaining. Key proteins involved in apoptosis, ER stress and autophagy were quantified by immunoblotting. ATR treatment resulted in Fas-mediated activation of caspases 8 and 3 and inactivation of PARP1 which were inhibited significantly by co-treatment with MEL. MEL also attenuated the ATR-induced, p53 independent mitochondrial apoptosis through upregulation of E2F-1 and PUMA and suppression of their downstream target Bax. An excessive ER stress triggered by ATR through overexpression of ATF-6α, spliced XBP-1, CREB-2 and GADD153 signals was reversed by MEL. MEL also reversed the ATR-induced impairment of autophagy which was indicated by a decline in BECN-1, along with significant enhancement in LC3B-II and p62 expressions. Induction of mitochondrial apoptosis, ER stress and autophagy dysregulation provide a new insight into the mechanism of ATR immunotoxicity. The cytoprotective role of MEL, on the other hand, was defined by attenuation of ER stress, Fas-mediated and p53 independent mitochondria-mediated apoptosis as well as autophagy signals.

28 citations


Journal ArticleDOI
TL;DR: There may be a functional parallelism between gonadal steroids and melatonin as melatonin is progonadotrophic in goats, and reproductive and immune seasonality are maintained by variations in circulatory hormones and local synthesis of melatonin and gonadal steroid.

21 citations


Journal Article
TL;DR: The data presented strong positive correlation between high levels of nighttime melatonin levels and immune parameters during winter suggests that melatonin possesses immunoenhacing as well as antioxidative property during winter.
Abstract: Daily variation in circulatory melatonin level, during different seasons, has been reported to influence immune system and free-radical scavenging capacity in mammals, including human beings Similar studies have not been carried out on small ruminant viz goats that are susceptible to opportunistic infections, increased oxidative load and sickness during free-grazing activity and frequent exposure to agro-chemicals Therefore, daily variation in immune status, antioxidant enzyme activity and its possible correlation with circulatory melatonin level during two different seasons, summer (long day) and winter (short day) were studied in the Indian goat, Capra hircus The clinically important immune parameters, such as total leukocyte count, % lymphocyte count and % stimulation ratio of T-lymphocytes presented a day/night rhythm prominently in the winter The oxidative load in terms of malonedialdehyde was always low during night while antioxidant enzymes superoxide dismutase, catalase and total antioxidant status were high during nighttime (1800 to 0600 hrs) Interestingly, the studied parameters were significantly higher during the winter in both the sexes Rhythmometric analyses showed prominent rhythmicity in above parameters The data presented strong positive correlation between high levels of nighttime melatonin levels and immune parameters during winter It suggests that melatonin possesses immunoenhacing as well as antioxidative property during winter This might be a necessity for maintenance of physiological harmony in goats to protect them from winter stress

16 citations


Journal ArticleDOI
01 Aug 2014-Zoology
TL;DR: Melatonin prevents/alleviates oxidative damage and suppresses the immune status induced by stressful conditions via its membrane receptor expression (Mel(1a) and Mel(1b)) in P. asiatica.

11 citations


Journal ArticleDOI
TL;DR: Exogenous melatonin treatment to hamsters enhanced the AA-NAT activity in spleen and thymus along with an increase in the inflammatory response by DTH reactions that could be related to the increased level of interleukin-2 and IFN-γ by T lymphocytes in serum/culture medium, proliferation rate and expression of melatonin membrane receptor MT(1).

10 citations


Journal ArticleDOI
TL;DR: Melatonin through its membrane receptor induced the elevation of Ca2+ i via IP3-dependent pathway for splenocyte proliferation in P. asiatica, suggesting a role for IP3 in the immune regulation of birds.
Abstract: Melatonin plays an important role in the immune regulation of birds. Both endogenous and exogenous melatonin modulates lymphocyte proliferation via its specific membrane receptors, Mel1a, Mel1b and Mel1c, though the mechanisms behind this process are poorly understood. We investigated the differences in melatonin membrane receptor Mel1a, Mel1b and Mel1c expression by western blot and reverse transcription reaction and the in vitro effect of melatonin on the intracellular Ca2+ concentration ([Ca2+]i) in splenocytes of the Indian Jungle Bush Quail, Perdicula asiatica. We used a non-selective melatonin receptor antagonist for Mel1a and Mel1b, luzindole, and the selective Mel1b blocker, 4P-PDOT to check the specific role of melatonin receptor on ([Ca2+]i). The expression of Mel1a, Mel1b and Mel1c receptors mRNA and protein was upregulated by melatonin (10−7 M) with a significant high rise in ([Ca2+]i), which was differentially blocked by supplementation of antagonist, luzindole (10−7 M) and 4P-PDOT (10−7...

9 citations


Journal ArticleDOI
TL;DR: For the first time, UVB radiation incurred oxidative damage to the spleen and suppressed the normal tissue functions and UVB mitigated oxidative stress was recovered by the free radical scavenging and anti-apoptotic functions of melatonin when administered prior to UVB irradiation.
Abstract: Tropical animals are regularly exposed to solar UV radiation. The generation and accumulation of free radicals as a result of UVB incidence causes tissue damage. In the present study we report that the irradiation of Funambulus pennanti by 1.5 J/cm2 of UVB caused significant oxidative damage to the spleen. The systemic immunity suffered collateral damage as depicted by results of total leukocyte count (TLC) while an increase in the thiobarbituric acid reactive substances (TBARS) and decline in the activities of enzymes superoxide dismutase (SOD), Glutathione peroxidase (GSH-Px) and Catalase (CAT) denoted oxidative tissue damage. Melatonin the indole-amine with known antioxidative properties when administered subcutaneously (s.c 100 μg/100 gm body weight), before the UVB irradiation recovered the damages caused by UVB radiation in the spleen. The action of melatonin was direct and might have involved its membrane receptor (MT1) as well as nuclear receptor (RORα) indicating the fact that the mode of action of melatonin in ameliorating UVB radiation induced free radical load may be receptor mediated. Our study hence reports for the first time that UVB radiation incurred oxidative damage to the spleen and suppressed the normal tissue functions. This UVB mitigated oxidative stress was recovered by the free radical scavenging and anti-apoptotic functions of melatonin when administered prior to UVB irradiation.

7 citations


Journal ArticleDOI
TL;DR: The observations suggest that the age-associated immunosenescence observed in goats can be a consequence of declining melatonin and its receptor expression and induction of apoptotic factors influenced by the increased RNS level that deteriorates the proper functioning of the spleen.

5 citations


Journal ArticleDOI
TL;DR: Investigation of daily/nycthemeral variation in expression of melatonin receptor subtypes MT1/MT2 in the lymphoid organs of a tropical squirrel suggests that there exists a temporal window of sensitivity in the target organs to the melatonin signal that is regulated by modulation ofMelatonin receptor expression which might be involved in mediating the photoperiodic effects ofmelatonin in the control of seasonal immune physiology.
Abstract: Seasonal variations in immune functions point toward the involvement of melatonin in its regulation. These chronobiotic effects are exerted by receptors present on the immunocompetent cells. The present study investigated daily/nycthemeral variation in expression of melatonin receptor subtypes MT1/MT2 in the lymphoid organs (spleen/thymus) of a tropical squirrel, Funambulus pennanti. The receptor expression was noted every 4 h interval over 24 h under natural light-dark cycle, during two seasons and was correlated with peripheral level of melatonin. The MT1/MT2 receptor expression displayed higher levels at the time of dusk (light-dark transition; 1800 hours), while plasma melatonin was still low compared to the preceding time point. The receptors were downregulated during the nighttime with a minimum expression at 0200 hours. Thymus, during the long day length, showed a tissue-specific pattern of receptor expression with a minimum expression at 0600 hours. Results suggest that photoperiod by modulation of melatonin level inversely regulates the receptor expression. The observations imply that there exists a temporal window of sensitivity in the target organs to the melatonin signal that is regulated by modulation of melatonin receptor expression which might be involved in mediating the photoperiodic effects of melatonin in the control of seasonal immune physiology.

Journal Article
TL;DR: The light microscopic and ultrastructural organization of HG of P. asiatica have been elucidated and it is found that the HG of this bird is encapsulated by thick connective tissue consisting of collagen fibers, nerve fibers and blood vessels.
Abstract: The structure of Harderian gland (HG) of tropical avian species has never been studied in detail. In the present study we investigated the structure of HG of a t ropical avian species adopting light- and transmission electron microscopy. HG from both male and female adult birds, P. asiatica (N=5 each sex) were studied from light microscopic (hematoxylin-eosin staining) and transmission electron microscopic perspectives. The tubulo-alveolar HG of P. asiatica did not reveal any sexual dimorphism as reported in other birds. The HG of this bird is encapsulated by thick connective tissue consisting of collagen fibers, nerve fibers and blood vessels. HG lobules are lined with columnar epithelial cells. Plasma cells are found in interlobular spaces. The columnar epithelial cells are secretory in nature and have both rough and smooth endoplasmic reticula surrounding the nucleus when observed in transmission electron microscope. There is active Golgi apparatus with dilated cisternae. Mitochondria are well developed, with elongated cristae, and are scattered throughout the cytoplasm along with abundant free ribosomes. Lipid droplets are present in the cytoplasm along with two types of materials, electron-luscent and electron-dense. We could trace the various stages of synthesis of the secretory material for merocrine release. Thus, the light microscopic and ultrastructural organization of HG of P. asiatica have been elucidated.


Journal ArticleDOI
TL;DR: It is concluded that not only the age but also the different causes of death may severely affect the basic micro-architecture of human pineal gland.
Abstract: Introduction In human, the age dependent changes in the micro-anatomy and histology of different organs are most prevalent along with causes of death. As pineal is a neuro-endocrine gland and is target of various hormones of physiological importance hence, the effect of age and different unnatural causes of death may affect its histology. This aspect of histomorphology has never been studied previously. Therefore, aim of the present study was to evaluate the changes in morphology and histology of human pineal gland in different age groups in relation to different causes of death. Methods We collected human samples from young (5–20 yrs), middle aged (21–55 yrs) and old aged (56–95 yrs) individuals under different causes of death like septicemia (S), poisoning (P), hanging (H), burning (B), injury (I) and other reasons which are regarded as control (C) and were processed for morphometric and histological observations. Results Anatomically significant decrease in pineal weight, length, breadth was noted in an age dependent manner. Histological observations suggest a significant increase in numbers as well as size in pineal concretions with increasing age. Further, huge degeneration of pinealocytes and neuronal glial cells was observed upon poisoning and burning cases in comparison to control. But in case of hanging, septicemia and injury there was no significant difference in comparison to control. Discussion It may be concluded that not only the age but also the different causes of death may severely affect the basic micro-architecture of human pineal gland.

Journal ArticleDOI
TL;DR: The data suggest that in this tropical rodent gonadotropins have an indirect effect on HG and that gonadal steroids have significant effect on HL through the influence on gonadal and pineal functions.
Abstract: Mostly studied in the hamster, the Harderian gland (HG, an extra-orbital gland) has been shown to be capable of melatonin (MEL) synthesis and to possess steroid receptor binding sites. Sexual dimorphism and ability to respond to steroid hormones have been reported for HG of some temperate zone mammals. However, to date there is no report on functional relation of HG with pineal, pituitary and gonad in any rodent. Hence, we tested the effect of gonadotropins [FSH (10μg) + LH (10μg)] and steroids [testosterone (100μg) and 17-β estradiol (50μg)] on HG function in relation to the activities of the pineal gland and gonad in both sexes of Indian palm squirrel Funambulus pennanti during the sexually quiescent phase. In general, squirrels treated with gonadotropins and gonadal steroids showed a significant increase in gonadal weight and decrease in pineal weight and plasma melatonin level in LH- and testosterone-treated groups only. There was no change in the weight of HG on FSH treatment. Porphyrin content of HG decreased after testosterone and estradiol treatment. Pineal gland weight invariably decreased after treatment with gonadotropins and testosterone. Plasma testosterone and estradiol levels increased but melatonin level decreased in all treated groups. Our data suggest that in this tropical rodent gonadotropins have an indirect effect on HG and that gonadal steroids have significant effect on HG through the influence on gonadal and pineal functions.

Journal ArticleDOI
TL;DR: Over all, administration of gonadal steroids to both male and female mice accelerated the gonadal recrudescence but did not inhibit the reproductive functions when administered during the RIP, which can be inferred from the present study that during theRIP the HPG axis is sensitive to Gonadal steroids and, hence, exogenous gonadal steroid induce gonadal activity.
Abstract: Different thresholds of gonadal steroids exert stimulatory or inhibitory effects on GnRH and gonadotropin release. During the reproductively active phase (RAP), the concentration of endogenous gonadal steroids remains high while, during reproductively inactive phase (RIP), it remains low. During RIP the HPG axis is sensitive to gonadal steroids but the circulatory levels of testosterone and estradiol remain low. During this phase one can observe conveniently the effects of gonadal steroids on the HPG axis in male or female rodents. Therefore, the aim of the present study was to find the effects of testosterone and estradiol on the reproductive functions of male and female Indian pygmy field mouse, Mus terricolor , during RIP. The male mice were injected aquaviron (commercially available testosterone, 1mg/100g body weight) while the female mice received estradiol-benzoate (25μg/100g body weight) for 15 consecutive days during the RIP. After completion of the treatment, a significant increase in the weights of gonads and accessory sex organs was noted in both the sexes. The biochemical constituents of accessory sex organs such as epididymal sialic acid, seminal vesicular fructose and uterine protein content reflected significant elevation accompanied by increased levels of plasma testosterone, estradiol and progesterone. Histologically, the gonads and accessory sex organs exhibited increased cellular activity. However, the gonadal cholesterol was significantly decreased in both the sexes. Over all, administration of gonadal steroids to both male and female mice accelerated the gonadal recrudescence but did not inhibit the reproductive functions when administered during the RIP. Therefore, it can be inferred from the present study that during the RIP the HPG axis is sensitive to gonadal steroids and, hence, exogenous gonadal steroids induce gonadal activity.