Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction

Although conventional chemotherapy has been successful to some extent, the main drawbacks of chemotherapy are its poor bioavailability, high-dose requirements, adverse side effects, low therapeutic indices, development of multiple drug resistance, and non-specific targeting. The main aim in the development of drug delivery vehicles is to successfully address these delivery-related problems and carry drugs to the desired sites of therapeutic action while reducing adverse side effects. In this review, we will discuss the different types of materials used as delivery vehicles for chemotherapeutic agents and their structural characteristics that improve the therapeutic efficacy of their drugs and will describe recent scientific advances in the area of chemotherapy, emphasizing challenges in cancer treatments.

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Controlled drug delivery vehicles for cancer treatment and their performance.

Textbook of histology

Natural and synthetic polymers for wounds and burns dressing

Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is mainly driven by the circadian clock, situated in the suprachiasmatic nucleus of the hypothalamus, which controls the release of norepinephrine from the dense pineal sympathetic afferents. The pivotal role of norepinephrine in the nocturnal stimulation of melatonin synthesis has been extensively dissected at the cellular and molecular levels. Besides the noradrenergic input, the presence of numerous other transmitters originating from various sources has been reported in the pineal gland. Many of these are neuropeptides and appear to contribute to the regulation of melatonin synthesis by modulating the effects of norepinephrine on pineal biochemistry. The aim of this review is firstly to update our knowledge of the cellular and molecular events underlying the noradrenergic control of melatonin synthesis; and secondly to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis. This information reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism. This also clarifies the role of these various inputs in the seasonal variation of melatonin synthesis and their subsequent physiological function.

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Effects of continuous light (CL; 24L : 0D), continuous darkness (CD; 24D : 0L) and pinealectomy (Px) were tested on pineal-thyroid-gonadal axis of a tropical seasonally breeding rodent, Funambulus pennanti during its sexually active reproductive phase (February–March). CL had no effect on pineal, thyroid and ovarian functions as judged by weight, plasma level of thyroxine (T4) and estradiol (E2). However, CD reduced significantly thyroid and ovarian weight and plasma T4, and E2 levels. Px was stimulatory for thyroid and ovarian functions under normal photoperiod, and under CL, Px significantly increased thyroid and ovarian weights with no observable changes in their hormonal levels. Px under CD condition prevented the reduction in thyroid and ovarian weights but the hormonal levels were increased. These results suggest that CD could be a effective stimulator for the pineal function and increased pineal activity in this mammal. The inhibitory effect of CD on thyroid and ovarian functions could be due to the increased pineal activity in term of induced melatonin by CD itself.

Effects of continuous light, continuous darkness and pinealectomy on pineal-thyroid-gonadal axis of the female Indian palm squirrel, Funambulus pennanti

BPS has detrimental effects on human reproductive health and emerged as an environmental contaminant for global health concern. This study deals with the adverse impact of BPS exposure on testicular oxidative stress, inflammation and apoptosis in adult male golden hamster, Mesocricetus auratus and its amelioration by melatonin. BPS (75 mg/kg BW/day) exposure caused testicular impairment as evident by histological degenerative changes, declined sperm quality (viability and motility), serum levels of testosterone and melatonin with a concomitant decrease in testicular androgen receptor (AR) and melatonin receptor (MT1) expression. The BPS exposure caused marked increase in testicular oxidative load, inflammation (NF-kB/COX-2) and apoptosis (caspase-3). Melatonin (10 mg/kg BW/alternate day) pretreatment to BPS exposed hamsters resumed normal testicular histoarchitecture, sperm quality and decreased testicular oxidative load as evident by enhanced antioxidant enzymes (SOD and catalase) activities and decreased lipid peroxidation (LPO) level. Further, melatonin also stimulated the testicular antioxidant proteins Nrf-2/HO-1, SIRT-1/FOXO-1 and reduced inflammatory proteins NF-kB/COX-2 expression to counteract BPS induced testicular damages. Melatonin administration to the BPS treated hamsters resulted in increased testicular cell proliferation (PCNA), survival (Bcl-2), gap junction (connexin-43) and decreased apoptosis (caspase-3). In conclusion, our study documented the detrimental effects of BPS on testes that compromises male fertility. Further, melatonin was found as a potent molecule that rescued the BPS induced testicular damages in male golden hamster Mesocricetus auratus.

Melatonin ameliorates Bisphenol S induced testicular damages by modulating Nrf-2/HO-1 and SIRT-1/FOXO-1 expressions.

Photoperiod, indoleamines, and ovarian responses in the Indian tropical jungle bush quail Perdicula asiatica

Data suggests that UV radiation causes oxidative damage of the cells due to the release of inflammatory cytokines which in turn generates reactive oxygen species (ROS) that damages lipids, proteins and DNA. On the other hand, melatonin a potent antioxidant from the pineal gland under most of the conditions acts as a free radical scavenger. Our data suggests that melatonin pre-treatment (s.c. injections) significantly protected the diurnal squirrels from oxidative damages caused by UVC irradiation of 1528 mJ cm(-2) that induced suppression of delayed type hypersensitivity (DTH) responses. It also protected the rodents from UVC radiation induced increase in thiobarbituric acid reactive substances (TBARS) levels in spleen accompanied with a significant decrease in Superoxide Dismutase (SOD) activity indicating the occurrence of superoxide anion mediated damages following UVC exposure. Melatonin administration reduced the radiation induced oxidative stress in the spleen tissue as analyzed by reduced lipid damages and higher SOD activity. Under in vivo (100 μg/100g body wt.) and in vitro (250 pg/10(6) cells) conditions, melatonin pre-treatment prevented spleen tissues and splenocytes from radiation induced cell death. In conclusion we may suggest that melatonin could be one of the potent antioxidant and radio protector that may reduce UV radiation induced toxicity to the cells and hence may be clinically important.

The oxidative damages caused by ultraviolet radiation type C (UVC) to a tropical rodent Funambulus pennanti: role of melatonin.

Our interest was to find out whether pineal gland and their by melatonin act as modulator of immunosenescence. Parachlorophenylalanine (PCPA) – a β adrenergic blocker, is known to perform chemical pinealectomy (Px) by suppressing indirectly the substrate 5-hydroxytryptamine (5-HT) for melatonin synthesis and thereby melatonin itself. The role of PCPA, alone and in combination with melatonin was recorded in immunomodulation and free radical load in spleen of young adult and aged seasonal breeder Indian palm squirrel Funambulus pennanti. Aged squirrel presented reduced immune parameters (i.e. total leukocyte count (TLC), Lymphocytes Count (LC), % stimulation ratio of splenocytes (% SR) against T cell mitogen concanavalin A (Con A), delayed type hypersensitivity (DTH) to oxazolone) when compared to young adult group. Melatonin administration (25 μg/100 g body mass/day) significantly increased the immune parameters in aged more than the young adult squirrel while PCPA administration (4.5 mg/100 g body mass/day) reduced all the immune parameters more significantly in young than aged. Combination of PCPA and melatonin significantly increased the immune parameters to the normal control level of both the age groups. TBARS level was significantly high in aged than the young group. PCPA treatment increased TBARS level of young and aged squirrels both while melatonin treatment decreased it even than the controls. Nighttime peripheral melatonin level was low in control aged group than the young group. Melatonin injection at evening hours significantly increased the peripheral level of nighttime melatonin, while combined injection of PCPA and melatonin brought it to control level in both aged and young adult squirrels. PCPA suppressed immune status more in aged than in adult by reducing melatonin level as it did chemical Px. Melatonin level decreased in control aged squirrels and so there was a decrease in immune parameters with a concomitant increase in free radical load of spleen. Decreased immune status can be restored following melatonin injection which decreased free radical load of spleen and suggest that immune organs of aged squirrels were sensitive to melatonin. Increased free radical load and decreased peripheral melatonin could be one of the reasons of immunosenescence.

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Chandana Haldar

Papers

Effects of continuous light, continuous darkness and pinealectomy on pineal-thyroid-gonadal axis of the female Indian palm squirrel, Funambulus pennanti

Melatonin ameliorates Bisphenol S induced testicular damages by modulating Nrf-2/HO-1 and SIRT-1/FOXO-1 expressions.

Photoperiod, indoleamines, and ovarian responses in the Indian tropical jungle bush quail Perdicula asiatica

The oxidative damages caused by ultraviolet radiation type C (UVC) to a tropical rodent Funambulus pennanti: role of melatonin.

Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine