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Graphical abstract, Highlights • Diabetes is both clinically as well as genetically multifaceted group of disorders characterized by high blood glucose level. • Hyperglycemic condition arises due to shortage of insulin secretion or resistance developed by the cells of body against the insulin binding on its membrane receptors, or it may be the combination of both. • Present study was designed to explore therapeutic efficacy of exogenous supplementation of melatonin and insulin against the diabetes induced alterations in hematological variables. • Combined administration of melatonin and insulin significantly restored the altered hematological variables towards the normal range., The aim of the present was to ameliorate the protective effect of exogenous melatonin and insulin against the diabetes induced alterations in the different hematological variables. Albino rats were administrated streptozotocin at the dose of 15 mg/kg for 6 days. Total 54 rats were randomly selected for the experimental purpose and were divided into two major groups. Group-1 consisting twenty four (24) and were further sub-divided into four (4) different groups viz. group-I served as normal control, group-II served as melatonin treated, group-III served as insulin treated and group-IV served as glibenclamide treated. Group-2 consisting thirty (30) rats were given streptozotocin (STZ) injection (15 mg/kg) for 6 days. After confirmation of diabetes by measuring blood glucose level, animals having blood glucose level above 250 mg/dl) confirmed as diabetic. Thirty (30) Diabetic rats were further subdivided into following sub-groups and were given different therapeutic treatments, Viz group-I served as Diabetic control, group-II treated with melatonin, group-III treated with insulin, group-IV given treatment of melatonin and insulin and group-V were given treatment of glibenclamide respectively. Diabetic rats showed modulation in all the studied hematological variables. Diabetic rats displayed significant decline in RBCs count, HB level and its associated indices (HCT, RDW, MCV, MCH, MCHC), WBCs and its related indices (polymorphs and lymphocytes) and platelet distribution width (PDW %) whereas platelet count showed significant increase. Nonetheless alone as well as combined treatment of exogenous melatonin and insulin restored all altered hematological parameters. However, significant recovery was found in the group in which combined dose of melatonin and insulin was administrated. Therefore, it might be concluded that combined administration of melatonin and insulin will be better remedy to normalize the altered blood profile during the diabetic condition.

Fil: Hajam, Younis Ahmad. Universidad Central Guru Ghasidas Vishwavidyalaya. Departamento de Zoología; India Fil: Hajam, Younis Ahmad. Universidad Career Point. Departamento de Biociencias. División de Zoología; India Fil: Rai, Seema. Universidad Central Guru Ghasidas Vishwavidyalaya. Departamento de Zoología; India Fil: Pandi-Perumal Seithikurippu R. Somnogen Canada Inc.; Canadá Fil: Brown, Gregory M. Univeridad de Toronto. Centro para la Adicción y la Salud Mental. Ciencias Moleculares del Cerebro; Canadá Fil: Pandi Perumal, Seithikurippu R. Universidad Saveetha. Instituto Saveetha de Medicina y Ciencias Médicas. Hospital Universitario Saveetha; India Fil: Reiter, R. Universidad de Texas. Departamento de Sistemas Celulares y Anatomía; Estados Unidos Fil: Cardinali, Daniel Pedro. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Abstract: Introduction: The present study was designed to evaluate the therapeutic efficacy of melatonin and insulin coadministration in diabetes-induced renal injury in rats. Research Design and Methods: Diabetes was achieved by giving streptozotocin (15 mg/kg) for 6 consecutive days. The diabetic condition was confirmed by assessing the blood glucose level; animals having blood glucose levels above 250 mg were considered as diabetic. Following the confirmation, animals were randomly divided into different experimental groups, viz group I served as the control (CON), group II diabetic (D), group III D+melatonin (MEL), group IV D+insulin (INS), group V D+MEL+INS, group VI D+glibenclamide (GB), group VII CON+MEL, group VIII CON+INS, and group IX CON+GB. Following the completion of the experimental period, animals were sacrificed, blood was collected via a retro-orbital puncture, and kidneys were harvested. Diabetic rats exhibited a significant increment in blood glucose and biochemical indexes of renal injury (tubular disruption, swollen glomeruli with loss of glomerular spaces, and distortion of the endothelial lining) including augmented levels of serum creatinine, urea, uric acid, Na+, and K+, and inhibition/suppression of the activity of glutathione (GSH) peroxidase, GSH reductase, glucose-6-phosphate dehydrogenase, and GSH-Stransferase in the renal cortex. Results: By examining thiobarbiturate reactive substances, reduced GSH, superoxide dismutase activity, and catalase activity in the renal cortex of control and diabetic rats, it was documented that treatment with melatonin or insulin alone or in combination showed a significant ad integrum recovery of GSH-dependent antioxidative enzymatic activities. Melatonin and insulin coadministration caused greater reductions in circulating tumor necrosis factor-α, tumor growth factor-β1, interleukin (IL)-1β, and IL-6 levels in diabetic rats, whereas IL-10 levels increased, as compared to each treatment alone. Diabetic rats showed a significant increase in the expression of both MT1 and MT2 melatonin receptor genes. Melatonin or insulin treatment alone or in combination resulted in significant restoration of the relative expression of both melatonin receptors in the renal cortex. Conclusion: The coadministration of exogenous melatonin and insulin abolished many of the deleterious effects of type 1 diabetes on rat renal function.

Background: Diabetes is one of the most challenging health problems in 21st century. It is a group of endocrine-metabolic disorder characterized by high glucose level (hyperglycemia) due to insufficient insulin secretion/action or both. It causes multi-organ failure viz hepatorenal damage, adult-onset blindness, lower-limb amputations, heart diseases and stroke, high blood pressure and nerve damage. Moreover, diabetic patients are having higher risk of cardiovascular complications including atherosclerosis, hypertension, lipoprotein abnormalities and cerebrovascular disease.Study design: Considering the potencies of currently available drugs for the treatment of diabetes and associated complications, present study was focussed to explore the role of plant bioactive components as alternative and easily accessible therapeutic remedies.Hypothesis/Purpose: This study the pooled status of diabetes, available treatments, attitude and traditional herbal polyphenols regarding diabetes.Results: This study was aimed to summarize the natural polyphenols having anti-diabetic, anti-inflammatory, anti-apoptotic and anti-cancerous activities. Polyphenols can decrease other metabolic diseases such as insulin resistance, hyperglycemia, hyperlipidemic, and obesity and Type-2 diabetes.Conclusion: Polyphenols are promising alternatives that can decrease the severity of diabetes and promote the other protective roles by decreasing the adverse effects of diabetes on other metabolic organs and their functions.

Background and objectives Polycystic ovary syndrome (PCOS) is a common heterogeneous endocrinological and metabolic disorder in women of reproductive age which leads to infertility/subfertility. The present study was commenced to elucidate the therapeutic efficacy of melatonin in the pathogenesis of letrozole induced polycystic ovary syndrome (PCOS) in Wistar rat. Materials and methods Letrozole was administered orally (1 mg kg-1) to induce PCOS condition in Wistar female rats for a period of 2-3 weeks followed by a dose of melatonin (200 µg/100 g b.wt.) to PCOS induced rats. On the completion of experimental period the level of cytokines and expression level of different receptors was assessed. Results The PCOs rats showed down regulation in melatonin (MT1 and MT2), estrogen (ER-α) and cytokine (IL-2R and IL-6R) receptors expression and high circulatory level of IL-6 and TNF-α during PCO condition. These anomalies in expression pattern and circulatory level of cytokines were restored following the treatment. Conclusion Finding of present study showed the role of melatonin supplementation at receptor level and also suggesting a crosstalk between MT1R / MT2R via cytokine IL-2R and IL-6R resulting in modulation of ER-α receptors.

Background and objective Hyperglycemia is a representative hallmark and risk factor for diabetes and is closely linked to diabetes associated complications. The aim of the present study was to evaluate the therapeutic potential of exogenous melatonin against the streptozotocin induced pancreatic damages in rats. Materials and methods Streptozotocin was injected for consecutive 6 days. Diabetes was confirmed by blood glucose measurement after 72 h and on 7th day after injection. Animals having blood glucose level above 250 mg dL-1 were considered as diabetic and were administered exogenous melatonin for 4 weeks. Animals were euthanized after last dose, pancreas were dissected out, weighed and fixed in Bouin's fixative for histology and further tissues were kept at -20°C for biochemistry. Results Diabetic rats displayed significant increase in lipid peroxidation, but pancreatic weight index, antioxidant system (GSH, SOD and CAT) showed decrease. Melatonin treatment to diabetic rats restored the alteration in physiological and biochemical markers. Results were supported by the histopathological observations, STZ treated pancreas showed damage in islets of langerhans, while as melatonin treated diabetic rats recovered the cellular architecture which inturn normalize the function of the pancreas. Conclusion Therefore, melatonin might be considered as a molecule to protect the pancreatic damages.

Diabetes is very common all over the world, but still not curable and controlled; it causes alteration in all over body. It needs serious concern for the scientific community to find out some control measures. The current work was planned to explore the possible defensive effect of melatonin against the diabetes induced changes in whole blood profile. For this study albino rats were treated with streptozotocin [(STZ) (15 mg/kg for 6 days)] to induce diabetes. Induction was confirmed by blood glucose and serum sugar assessment. Total 36 rats were randomly selected for the experimental purpose and were divided into two major groups. Major group-1 consisting eighteen (18) and were further sub-divided into three (3) different groups viz. group-I served as normal control, group-II served as melatonin treated, group-III served as glibenclamide treated. Major group-2 consisting eighteen (18) rats were given streptozotocin (STZ) injection (15 mg/kg) for 6 days. After confirmation of diabetes by measuring blood glucose level, animals having blood glucose level above 250 mg/dl) confirmed as diabetic. Eighteen (18) Diabetic rats were three subdivided into following sub-groups and were given different therapeutic treatments, Viz group-IV served as Diabetic control, group-V treated with melatonin, group-VI treated with glibenclamide, respectively. Diabetic rats demonstrated inflection in all hematological variables. Diabetic animals revealed considerable reduction in RBCs count, HB content and its associated indices (HCT, RDW, MCV, MCH and MCHC). Decrease in WBCs and its related indices (polymorphs and lymphocytes). Platelet count showed significant increase, but platelet distribution width (PDW %) was found decreased. However administration of melatonin restored all the alterations in hematological parameters. Therefore, it can be concluded that melatonin will be better therapeutic molecule to revive hematological alterations during diabetes., Biocheminstry; Food science; Veterinary medicine; Health sciences; Diabetes, Melatonin, Hematology, Hepatorenal, Antioxidative status, Biochemistry, Streptozotocin, Blood glucose, Protection.

The objective of present study was to establish the interrelationship between thyroid and melatonin during anovulatory/letrozole induced polycystic ovarian condition on female Wister rats. Rats were procured and after acclimatization 20 rats were divided in 4 groups with 5 rats in each. They were divided as Control, Letrozole induced PCO rat (1 mg/kg BW/d), and melatonin alone (200 μg/100 g BW/d). The experiment was conducted for the duration of 28 d. Assessment of gravimetric, hormonal profile and thyroid histology and relative expression of MT1, MT2, and ERα, (thyroid, ovary) Dio2, TRα (Ovary) done followed by standard protocol. Histological observation showed shrinkages in thyroid follicles in PCO rats however exogenous melatonin maintained the cellular architecture and normal thyroid weight. PCO rats showed significantly high circulating testosterone but significant decreased in estrogen and progesterone level. Circulatory gonadotropins (LH, FSH) were noted significantly high in PCO rats. Melatonin injection to the PCO rats however reversed to the control level and restored. Circulatory TSH level in PCO rats were noted suppressed where as T3 and T4 were non-significantly increased suggesting a reciprocal relation between melatonin and thyroxine. Thyroid tissue of PCO rats expressed MT1 and MT2 in way alternate and opposite way being MT1 as up regulated whereas down regulation of MT2. Ovarian tissue of PCO rats showed reverse receptor expression to that of thyroid tissue being MT1 down regulated and MT2 was noted unregulated. Parallel relation was noted between ERα and TRα receptor expression in thyroid and ovarian tissue respectively. PCO rats resulted in up regulation of Dio2, receptor expression in a non-significant manner. Therefore, present finding suggests a fine interplay and cross talk via melatonin its two receptor MT1 , MT2 with ERα, TRα, and Dio2 thyroid and ovarian tissue as the case between ovarian thyroid axis hence maintaining a physiological trade-offs between theses gland with a tonic regulation to maintain melatonin and thyroid homeostasis during polycystic pathogenicity.

Objective: To evaluate the therapeutic efficacy of exogenous melatonin (MEL) on hepato-renal tissue in a diabetic rat model. Methodology: Streptozotocin (STZ) was used to establish diabetic rat model. Diabetes was confirmed by monitoring the blood glucose level, animals having glucose level above 250 mg/dl were considered as diabetic and were divided into six different groups. Model control group, diabetic group, melatonin treatment to diabetic rats, melatonin per se group, glibenclamide (a standard hypoglycemic drug) treatment to diabetic rats and glibenclamide (standard control) alone respectively. The model control was given 0.5 ml (0.1 M) citrate buffer, experiment was conducted for one month. After the completion of experiment, rats were sacrificed. Blood was collected and centrifuged at 3000 rpm for 10 minutes to obtain the serum. Serum was kept at -800c for further analysis of liver and renal function tests and lipid profile. Liver and kidney tissues were weighed, fixed in Bouin’s fixative for histopathological studies. Further tissues were processed for Lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT). Major findings: Administration of MEL to STZ induced diabetic rat showed a significant decrease of lipid peroxidation (TBARS) in kidney and liver tissue comparable to the control and GLIBEN group of rats. In addition MEL prevented the decrease in antioxidative enzyme parameters viz. superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) of hepato-renal tissues. Parameters of liver functions (alanine amino transaminase (ALT), aspartate amino transaminase (AST) and alkaline phosphatase (ALP) and renal function (urea, uric acid and creatinine) were noted restored following MEL treatment. MEL administration further maintained the normal levels of lipid profiles i.e., triglyceride, cholesterol, low and high density lipoprotein (LDL, HDL) to that of the control group of rats. Histological architecture of liver and kidney tissues were noted repaired and rescued as judged by cellularity of hepatocytes and renal cells. Conclusion: The present finding strongly indicates the protective effect of exogenous melatonin for hepato-renal tissues form the damages and impairment observed and noted in the experimentally induced STZ male rat model.

Objectives: The present study was designed and conducted for obtaining information about the role of melatonin (Mel) in pathophysiology of polycystic cystic ovarian syndrome (PCOS) which generally leads to infertility in human females.Methodology: Letrozole, a non-steroidal aromatase inhibitor supplemented (1 mg/100 g/body weight/day for 28 days) for induction of (PCOS). Treatment of exogenous melatonin (200 μg/100 g/body weight/day) was given to PCO and normal rats. After completion of experiment gravimetric analysis, Lipid peroxidation (LPO) in terms of thiobarbituric acid reactive substance (TBARS), histological slide preparation following hemotoxylene-eosin (HE) double staining method for ovarian tissue was done and results were documented. Hormonal assay estrogen (E), progesterone (P), and Melatonin (Mel), luteinizing hormone (LH) and follicle stimulating hormone (FSH) was performed using ELISA kit.Major findings: Letrozole induced PCOS exhibited increase in ovarian weight, lipid peroxidation level (LPO). Histopathology of PCO rats showed sub-capsicular cysts and capsicular thickening. Circulatory hormone profiles showed a significant decrease in plasma level of E, P, Mel. Plasma testosterone (T) level was noted significantly high whiles an unsteady ratio of LH) and FSH in PCOS rats. Melatonin treatment to the PCO rats showed recovery in ovarian weight, significant decrease in lipid per oxidation (LPO), withdrawal of presence of cyst from ovarian histology, reversal of plasma circulatory hormone profile to the control group of rats.Conclusion: The finding update about similarity of ovarian cysts in rats to that observed in human PCOS and their regression following exogenously melatonin administration. The present findings may indicate and novel therapeutic approach based on the modulation of pathogenicity of PCOS in female rats through melatonin to improve the functional ovarian physiology as a possible future molecule among human females to treat the infertility. Such clinical trials may really prove to be highly beneficial for women with PCOS.