Ameliorative Effect Of Melatonin Research Articles

Chronic Toxic Effects of Tramadol on the Brains of Adult Albino-Rats and possible Ameliorative Effects of Melatonin

Chronic Toxic Effects of Tramadol on the Brains of Adult Albino-Rats and possible Ameliorative Effects of Melatonin

Ameliorative effect of Melatonin on 5-Fluorouracil-induced reproductive toxicity in male rats.

5-Fluorouracil (5-FU) is an antimetabolite chemotherapeutic agent that can cause oxidative stress and complications in normal organs, including the reproductive system. This study was conducted to investigate the effect of melatonin (MEL) on 5-FU-induced reproductive toxicity in male rats. Male Wistar rats weighing 180 ± 20g were divided into five groups: control, 5-FU (50mg/kg), 5-FU + MEL (2.5, 5 & 10mg/kg). The testes and prostates were removed, and histopathological aspects, biochemical markers, and gene expression were investigated. The effect of 5-FU on the normal TM4 cell line (murine testicular Sertoli line) and co-treatment of 5-FU and MEL were studied using MTT assay. Results showed that MEL prevented cell death in the TM4 cell line induced by 5-FU. MEL also reduced edema, hyperemia, and vacuolization in testis and prostate tissues induced by 5-FU. Additionally, MEL increased the activity of antioxidant enzymes and reduced the levels of MDA (p < 0.0001) and MPO (p < 0.0001). The levels of testosterone (p < 0.01) and the number of spermatocytes and spermatogonia (p < 0.0001) were increased in groups receiving 5-FU with MEL compared to 5-FU alone. The prostate-specific antigen (PSA) level in prostate samples was lower in the groups receiving 5-FU with MEL compared to the 5-FU group. Furthermore, the genes expression of COX-2 and TNF-α in testis tissues was reduced in the presence of MEL. in conclusion, the antioxidant property of MEL can protect the male reproductive system against 5-FU toxicity, as evidenced by the improved histopathological and biochemical parameters, as well as the reduced gene expression of COX-2 and TNF- α genes.

Ameliorative effect of melatonin on different tomato genotypes to induce heat stress tolerance by modulating growth and physiological attributes

Ameliorative effect of melatonin on different tomato genotypes to induce heat stress tolerance by modulating growth and physiological attributes

Studies on melatonin intervention in reactive oxygen species-linked autophagy of neocarzinostatin-induced varicocele infertility in male Swiss Albino mice

BackgroundVaricocele is known to be a condition involving the impairment of spermatogenesis, thereby leading to low sperm production and decreased sperm quality and ultimately one of the major cause of male infertility. Melatonin has shown to directly neutralize a number of free radicals responsible for toxicity in the cell. PurposeTherefore, this, study is designed to evaluate the induction of varicocele following neocarzinostatin treatment and also to investigate possible ameliorative effect of melatonin against varicocele induction. MethodIn this study, male albino mice (aged 6 weeks and weighing 25 gs) were divided into eight groups (n = 10). Group I (Control), Group II -Varicocele (Positive Control), Group III -NCS (5 mg/kg.bwt), Group IV -NCS (10 mg/kg.bwt), Group V - NCS (20 mg/kg.bwt), Group VI- Varicocele + Melatonin (10 mg/kg.bwt), Group VII -NCS (10 mg/kg.bwt) + Melatonin (10 mg/kg.bwt), Group VIII -NCS (20 mg/kg.bwt) + Melatonin (10 mg/kg.bwt). Intraperitoneal injection of a mixture of ketamine and xylazine was administered into each mouse in group II and served as the positive control. Group III, IV and V received 5, 10 and 20 mg/kg.bwt of Neocarzinostatin daily respectively. Five mice from each group was sacrificed 24 hour (h) after the twenty-eight days treatment for further experiments while the remaining animals were used for fertility study. ResultsAt the end of the experiment, NCS treatment for 28 days reduced the body weight significantly decreased across the groups in a dose dependent manner (group II, III, IV, VI, VII and VIII). Swollen of the testis and enlarge blood vein were observed confirming the induction of varicocele by NCS-treated groups. Tubular Differential index (%) and Johnsen score (%) significantly reduced (p < 0.001) (p < 0.05). The levels of reactive oxygen species and malondialdehyde significantly increased (p<0.001) (p<0.05). The activities of glutathione, superoxide dismutase and catalase significantly reduced (p < 0.001) (p < 0.05). The level of Luteinizing Hormone, FSH and testosterone significantly reduced (p < 0.001) (p < 0.05). ConclusionIn conclusion, the results of this present study clearly showed that neocarzinostatin treatment leads to induction of varicocele infertility. Also, this study gives an insight that co-treatment of melatonin is able to reduce the hazardous effect of neocarzinostatin-induced varicocele and cytotoxicity in the testis of mice.

Hepatotoxic Effect of Hydrogen Cyanamide (Dormex®) in Albino Rats and the Ameliorative Effect of Melatonin

Background: Hydrogen cyanamide (Dormex®) is used as a fertilizer sprayed on fruits, especially grapes to stimulate buds’ opening. It causes oxidative stress leading to hepatic, renal, and lung damage. Melatonin is derived primarily from the amino acid tryptophan, produced from the pineal gland, and has antioxidant effects. This study aimed to examine the effects of acute hydrogen cyanamide (Dormex®) exposure on the liver of albino rats and evaluate the biochemical and histological changes caused by Dormex® toxicity. Additionally, the study evaluated the potential ameliorative role of melatonin in these harmful effects. Methods: Forty adult male albino rats were divided into four groups; group I: Negative control, group II: Melatonin-treated (100 mg/kg/day), group III: Dormex®-treated (100 mg/kg) as a single dose, and group IV: Receiving melatonin (100 mg/kg/day)+Dormex® (100 mg/kg). After 24 hours, all animals were evaluated for liver enzymes (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin), hepatic markers for oxidative stress (malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD)) and histopathological examination was done for hepatic tissues. Results: The Dormex®-treated group showed significantly elevated liver enzymes, elevated MDA, and decreased GSH and SOD. Histopathological examination revealed normal structure in groups 1 and 2 while group 3 showed several histopathological changes characterized by inflammation and hepatic necrosis. Administration of melatonin with Dormex® in group 4 caused a decrease in liver enzymes and MDA and an increase in GSH and SOD with improvement in liver histopathology. Conclusion: Melatonin showed an ameliorative effect and can be used as a protective agent against Dormex®-induced hepatic injury.

Protective effect of melatonin on learning and memory impairment and hippocampal dysfunction in rats induced by high-fructose corn syrup.

We investigated the harmful effects of high fructose corn syrup (HFCS) on learning and memory in the hippocampus and the ameliorative effects of melatonin (Mel). Thirty-six adult male Sprague Dawley rats were divided into three groups: Group I, control; Group II, HFCS; and Group III, HFCS+Mel. HFCS form F55 was prepared as a 20% fructose syrup solution. Rats in HFCS and HFCS+Mel groups were given drinking water for 10 weeks. Rats in the HFCS+Mel group have been given 10 mg/kg/day melatonin orally for the 6 weeks, in addition to HFCS 55. The Morris water maze (MWM) test was applied to all animals for 5 days to determine their learning and memory levels. After decapitation, one-half of the hippocampus samples were collected for western blot analysis, and another half of the tissues were collected for histopathological and immunohistochemical analyses. In the HFCS group, there was a significant difference between the time to find the platform in the MWM test and time spent in the quadrant between days 1 and 5 (P=0.037 and P=0.001, respectively). In addition, a decreased level of MT1A receptor, TNF-α, iNOS, osteopontin (OPN), and interleukin-6 (IL-6) expressions were significantly increased in the HFCS group. Melatonin treatment reversed MT1A receptor levels and TNF-α, iNOS, OPN, and IL-6 expressions. During the histopathological examination, increased neuronal degenerations were observed in the HFCS group. Melatonin ameliorated these changes. Consumption of HFCS caused deterioration of learning and memory in adult rats. We suggest that melatonin is effective against learning and memory disorders.

Toxic effects of excess exposure to boric acid on serum biochemical aspect, hematology and histological alterations and ameliorative potential role of melatonin in rats

The current work clarifies the negative effects of excess exposure to boric acid (H3BO3) as a boron-containing compound on rats and the possible ameliorative effect of melatonin (MEL). Forty rats were equally divided into 5 groups as follows: group 1 was treated as control while groups 2, 3, 4 and 5 were orally administered corn oil (0.5 ml), H3BO3 (1330 mg/kg BW), MEL (10 mg/kg BW) and H3BO3 + MEL for 28 consecutive days, respectively. At the end of the experiment, blood was sampled for biochemical and hematological analysis and tissues were collected for histopathological examination. The obtained results demonstrated that the exposure to H3BO3 induced hepatorenal dysfunctions, alterations in bone-related minerals and hormones levels, prostaglandin E2 as inflammatory mediator and hematological indices. H3BO3 induced histological alterations in the liver, kidneys, bone and skin. The co-administration of MEL with H3BO3 resulted in a significant improvement in most of the measured parameters and restoration of morpho-functional state of different organs compared to the H3BO3 group. In conclusion, the study clearly demonstrated that H3BO3- induced various adverse effects and that melatonin may be beneficial in a partial mitigating the H3BO3 and may represent a novel approach in the counteracting its toxicity.

Ameliorative effect of melatonin against storage chilling injury in pomegranate husk and arils through promoting the antioxidant system

Pomegranate is a tropical and subtropical fruit sensitive to chilling injury during its cold storage, leading to quantitative and qualitative losses, as well as reduced economic value. Recently, melatonin has been considered as an environmentally friendly treatment to maintain the postharvest quality of horticultural products. In this study, the effect of melatonin treatment on chilling tolerance, postharvest quality and antioxidant system of pomegranate fruit was investigated during storage at 4 °C for 120 days. According to the results, pH, titratable acidity and the total soluble solids of the fruit were not influenced by applying melatonin. However, melatonin treatment at 100 μM dramatically improved chilling tolerance in the pomegranate fruit by reducing electrolyte leakage and increasing the total phenol content, as well as the antioxidant potential. Melatonin significantly reduced polyphenol oxidase (PPO) activity and increased the activity of phenyl alanine amylase (PAL), catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD) enzymes in the husk and arils of the pomegranate fruit during storage. In addition, melatonin inhibited H2O2 accumulation in the pomegranate fruits. Therefore, our data suggest that melatonin might be useful in improving the postharvest quality and inducing chilling tolerance in pomegranates during the cold storage.

Ameliorative effects of melatonin and zinc oxide nanoparticles treatment against adverse effects of busulfan induced infertility in male albino mice

Testicular damage is one of the most hazardous effects as it’s associated with azoospermia. Busulfan (Bu) is a highly toxic chemotherapeutic drug that affects testis. Thirty male Swiss albino mice divided into six groups of 5 animals each. Control (oral 0.9% saline daily for 75 days); Mel (20 mg/kg/day orally for 30 days); ZnO NPs (5 mg/kg/day i.p. for 30 days); BU (single i.p. injection of 40 mg/kg and then left for 45 days); BU + Mel (single 40 mg/kg dose of BU and left for 45 days followed by 20 mg/kg/day Mel for 30 days); BU + ZnO NPs (single dose of 40 mg/kg of BU and left for 45 days, then 5 mg/kg/day ZnO NPs for 30 days). Preparation and Characterization of ZnO NPs. Specimens from testis prepared for ultrastructural investigations using TEM after Masson’s trichrome and toluidine blue staining. BU induced histological and ultrastructural damage of the testis. Moreover, the present results could be concluded that Mel or ZnO NPs can protect the testicular tissue against ultrastructural alterations induced by BU by its antioxidant and anti-apoptotic effects.

The ameliorative effect of melatonin on LPS-induced Sertoli cells inflammatory and tight junctions damage via suppression of the TLR4/MyD88/NF-κB signaling pathway in newborn calf

The blood-testicular barrier (BTB) is involved in spermatogenesis, protects sperm development, and plays a crucial role in the reproductive process. Tight junctions (TJs) between Sertoli cells (SCs) are the key structure of (BTB), and if its structure is damaged, BTB function is affected. The cellular inflammation caused by Gram-negative bacteria affects the structural integrity of TJs. Melatonin (MT) has anti-inflammatory effects; however, the effect of MT in newborn calf SCs is unknown. Therefore, this experiment studied the protective effect of MT. The results showed that LPS upregulated TLR4, MyD88, and NF-κB expressions, in turn, activated the TLR4/MyD88/NF-κB signaling pathway, produced a large amount of IL-6 and IL-1β, downregulated the expression of ZO-1 and Occludin, and reduced the viability of SCs, which resulted in the inflammatory response of SCs and damage of TJs. The addition of MT decreased TLR4, MyD88, and NF-κB expressions, it then inhibited the activation of TLR4/MyD88/NF-κB signaling pathway, downregulated the expression of IL-6 and IL-1β, upregulated the expression of ZO-1 and Occludin, and increased the cell viability, thereby alleviating the inflammatory response of SCs, and restored the TJs structure. Overall, our results reveal that MT can alleviate LPS-induced in newborn calf SCs Inflammation and TJs injury through TLR4/MyD88/NF-κB signaling pathway.

An insight into the ameliorative effects of melatonin against chromium induced oxidative stress and DNA damage: a review

Chromium (Cr), a ubiquitous metal, has become a potent pollutant due to global industrialization, leading to pollution of air, water, and food that impacts human health. The most stable forms of Cr are Cr(III) and Cr(VI) (the major product of industrial activities). Cr(III) is a micronutrient essential for maintaining normal blood glucose and lipid profiles in our body but it can also form Cr (III)-DNA adducts. In addition, it directly produces reactive oxygen species (ROS) via Fenton and Haber-Weiss reactions; leading to tissue injuries. Cr (VI) has the capacity to generate Cr(V), Cr (IV), and Cr(III), respectively under suitable conditions. These intermediates also damage to biological macromolecules by interactions with several enzymatic and non-enzymatic antioxidants. For example, Cr(III) can make double DNA strands breaking to inhibit DNA replication, induce DNA oxidation, and DNA adducts formation. All of these lead to the development of malignancy. Melatonin, a potent radical scavenger as well as a metal chelator, effectively chelates Cr(VI) and prevents DNA oxidative damage. Melatonin can upregulate the gene expression of several antioxidant enzymes, and thereby, maintains cellular integrity from the oxidative stress. Thus, melatonin can be a prime molecule to protect against Cr(VI) induced cytotoxicity and genotoxicity. This review aims to highlight the potential benefits of melatonin on Cr(VI) induced oxidative stress and DNA damage.

Melatonin Enhances Seed Germination and Seedling Growth of Medicago sativa Under Salinity via a Putative Melatonin Receptor MsPMTR1.

Alfalfa (Medicago sativa L.) is an important forage crop, and salt stress is a major limiting factor in its yield. Melatonin (MT) is a multi-regulatory molecule in plants. We showed that basal MT content was positively correlated with the salt tolerance degree of different alfalfa varieties. MT and its precursor 5-HT fully recovered seed germination while partially ameliorated seedling growth of salt-stressed alfalfa. The 5-HT showed some divergent effects from MT with regards to growth amelioration under salinity. Salt stress caused stunted plant growth in soil culture, while MT ameliorated it by elevating plant height, fresh weight, branching number, and chlorophyll content. Silencing of a putative MT receptor, MsPMTR1, which was shown to be membrane-localized, abolished the ameliorative effects of MT on salt-stressed alfalfa seedling growth, while overexpression of MsPMTR1 improved plant growth under salt stress. The RNA sequencing analysis showed that nine pathway genes were specifically induced by MT treatment compared with salt stress. These MT-responsive differentially expressed genes include basal metabolic pathway genes, such as “ribosome, elongation factor,” “sugar and lipid metabolism,” and “photosynthesis” and stress-related genes encoding “membrane integrity” related proteins, heat shock protein, peroxidase/oxidoreductase, and protease. Several abiotic stress response-related genes, such as DRE, ARF, HD-ZF, MYB, and REM were repressed by NaCl treatment while induced by MT treatment. In summary, we demonstrated the importance of MsPMTR1 in MT-mediated salt tolerance in alfalfa, and we also analyzed the regulatory mechanism of MT during alfalfa seed germination under salt stress.

Ameliorative effects of melatonin on intestinal oxidative damage in streptozotocin-induced diabetic rats

Background and Aims: The potential therapeutic effects of melatonin on changes in intestinal tissue of diabetic rats were investigated. Methods: Male Sprague-Dawley rats were assigned into 5 groups (10 rats in each): Control, diabetes, diabetes+insulin, diabetes+melatonin, and diabetes+insulin+melatonin groups. Streptozotocin (60 mg/kg) was administered intraperitoneally to the rats to induce diabetes. At the end of 8 weeks of treatment, after blood glucose measurement and subsequent decapitation, glutathione (GSH) and malondialdehyde (MDA) levels and caspase-3, myeloperoxidase (MPO), and superoxide dismutase (SOD) activities in the intestinal tissue were investigated. Results: In diabetic animals, elevated blood glucose levels caused oxidant damage in the intestinal tissue that was demonstrated with increased MDA levels, caspase and MPO activities, and decreased GSH levels and SOD activities. Although melatonin demonstrated more significant results than insulin, separate administration of both melatonin and insulin improved the oxidative damage parameters compared to the diabetes group. In the combined treatment group, all parameters were back to control levels statistically more significant when compared with the treatment-alone. Conclusion: Melatonin has been shown to protect intestinal tissue from diabetic oxidant damage. With insulin treatment in type I diabetes, melatonin supplements may increase the quality of life through reducing complications.

Ameliorative effect of melatonin on apoptosis, DNA fragmentation, membrane integrity and lipid peroxidation of spermatozoa in the idiopathic asthenoteratospermic men: In vitro.

Fertility loss, recurrent spontaneous abortion and poor outcome in assisted reproductive techniques (ART) have been associated with DNA fragmentation. This work was achieved to evaluate the protective role of melatonin versus apoptosis, DNA fragmentation, membrane integrity and lipid peroxidation of spermatozoa from men with asthenoteratozoospermia (ATS). Some researchers maintain that melatonin can serve as a remedy for apoptosis induction, and it has an impressive effect on boosting the quality and quantity of spermatozoa. For this purpose, semen samples were collected from 50 ATS men and they were divided into control and melatonin (6mM) groups at 2, 4, 6 and 24hr. Concentrating on the reasons for apoptosis is an arduous process, but in the present study for this evaluation mitochondrial membrane potential (MMP), DNA fragmentation by TUNEL and sperm chromatin dispersion (SCD) methods and lipid peroxidation were carried out. Also, sperm viability was performed. In the control group, MDA, TUNEL-positive and SCD were significantly increased but viability and MMP of spermatozoa were significantly decreased. Moreover, in the melatonin group, TUNEL-positive, SCD and MDA levels were significantly decreased and viability and MMP significantly increased, compared to the control group. In outcome, melatonin prescription paves the way for apoptosis down-regulating in the ATS men.

Melatonin and garlic cytoprotective-ameliorative effects on dibutyl phthalate intoxication on sperm DNA and testicular biomakers of rabbits

The study investigated the cytoprotective and ameliorative effects of melatonin and Allium sativum (garlic) on dibutyl phthalate (DBP)-induced oxidative stress, its impact on sperm DNA integrity and testicular oxidative stress biomarkers. Forty two rabbit bucks were randomly divided into 7 groups of 6 bucks each labeled as A, B, C, D, E, F and G: The treatment were as follows: A (served as negative control, received olive oil for 16 weeks); B (served as positive control, exposed to DBP for 16 weeks, no treatment); C (given melatonin for 8 weeks, thereafter DBP for 8 weeks); D (administered garlic for 8 weeks, thereafter DBP for 8 weeks); E (exposed to DBP for 8 weeks, thereafter melatonin for 8 week); F (exposed to DBP for 8 weeks, thereafter garlic for 8 weeks); and G (exposed to DBP for 8 weeks, thereafter melatonin + garlic for 8 weeks). Ejaculated semen was collected on the last day (112th) using artificialv vagina for rabbit and pooled for each group was used for sperm DNA fragmentation index (SDFI) determination, rabbits were sacrificed and the testes harvested for determination of superoxide dismutase activity, reduced glutathione and malondialdehyde concentration. Results showed a significant increase (P = 0.0018) in the mean SDFI in group B (78.20 ± 4.72), compared to other groups. A significant increase (P ≤ 0.0001) in superoxide dismutase activity, increase reduced glutathione concentration and decrease malondialdehyde concentrations in the treatment groups compared to the DBP exposed group without treatment (group B) were observed. Melatonin and garlic demonstrated cytoprotective and ameliorative effects against DBP-induced oxidative stress in rabbit bucks.&#x0D; Keywords: Dibutyl phthalate, Garlic, Melatonin, Sperm DNA, Testicular biomarkers

Ameliorative Effect of Melatonin Against Reproductive Toxicity of Tramadol in Rats via the Regulation of Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis-related Gene Expression Signaling Pathway.

BackgroundThe aim of the present study was to investigate the protective properties of melatonin (MT) against oxidative stress, mitochondrial dysfunction, and apoptosis induced by tramadol-reproductive toxicity in male rats.MethodsThe rats were divided into the 7 groups of control, melatonin (1.5 mg/kg), tramadol (50 mg/kg), and melatonin (1, 1.5 and 2.5 mg/kg) administered 30 minutes before tramadol and vitamin C group (100 mg/kg). All injections were performed intraperitoneally. After administration for 3 consecutive weeks, the animals were killed and testis tissues were used for assessment of oxidative stress markers including lipid peroxidation (LPO), glutathione (GSH) content and protein carbonyl (PrC), and sperm analysis. Mitochondria were isolated from rat’s testis using differential centrifugation technique and were studied in terms of mitochondrial viability, mitochondrial membrane potential (MMP), and mitochondrial swelling. The other part of the tissue sample was placed in RNA protector solution for assessment of Bax and Bcl-2 gene expression through real-time polymerase chain reaction (real-time PCR) assay.FindingsTramadol caused a significant decline in epidermal sperm count, motility, and morphology, as well as a significant decrease in GSH level and mitochondrial function, and a significant evaluation of LPO, PrC, MMP, and mitochondrial swelling. In addition, tramadol induced a significant decrease in Bcl-2 gene expression, and increase in Bax gene expression. However, pretreatment of rats with MT improved sperm analysis, and testicular antioxidative status, and mitochondrial function. Furthermore, MT pretreatment regulated testicular Bcl-2 and Bax expressions.ConclusionConsidering the protective effects of MT against reproductive toxicity induced by tramadol, this compound can be used as a possible agent for the prevention and treatment of tramadol-induced reproductive toxicity.

Effects of co-administered melatonin, fructose and bisphenol A (BPA) on rat epididymis and sperm characteristics

ABSTRACTConsumption of fructose-rich food and exposure to endocrine disrupting chemicals continue to increase. High fructose consumption is associated with increased incidence of dyslipidemia, hypertension, hyperuricemia and insulin resistance. Bisphenol A (BPA) is an environmental contaminant that exhibits estrogen-like activity; it impairs reproductive organs, sperm production, spermatogenesis and fertility. We investigated the possible ameliorative effects of melatonin on rat epididymis and sperm characteristics following exposure to fructose and BPA. We used 42 adult male Sprague-Dawley rats divided into seven groups. Group 1, control group, was treated with 25 mg/kg sesame oil + 25 mg/kg 0.1% ethanol. Group 2 was treated with 10% aqueous fructose. Group 3 was treated with 25 mg/kg BPA. Group 4 was treated with 10% fructose and 25 mg/kg BPA. Group 5 was treated with 10% fructose and 20 mg/kg melatonin. Group 6 was treated with 25 mg/kg BPA and 20 mg/kg melatonin. Group 7 was treated with 10% fructose, 25 mg/kg BPA and 20 mg/kg melatonin. After 60 days, epididymal tissue was removed and analyzed using histochemistry and immunohistochemistry. Sperm were counted, and sperm motility and viability were investigated. Administration of BPA caused significant damage to both epididymal tissue and sperm quality; melatonin reduced the damage, but did not prevent it completely.

Ameliorative effects of melatonin against solid Ehrlich carcinoma progression in female mice.

The current work estimated the antitumour efficacy of melatonin (MLT) on the growth of Ehrlich ascites carcinoma cells inoculated intramuscularly into the hind limbs of female BALB/c mice and to compare its effects with those of adriamycin (ADR). After solid tumours developed, the animals were divided into the three following groups: the tumour-bearing control, MLT-treated (20mg/kg body weight) and ADR-treated (10mg/kg body weight) groups. The results showed a significant reduction in the tumour masses of the treated animals in comparison with those of the control group. There were a significant decrease in the malondialdehyde level and a significant elevation of the glutathione concentration and the superoxide dismutase and catalase activities in the MLT and ADR groups. The current study indicated the increased expression levels of P53, caspase-3 and caspase-9 and the decreased expression levels of the rRNA and Bcl2. The MLT and ADR treatments resulted in histological changes, such as a marked degenerative area, the necrosis of neoplastic cells, the appearance of different forms of apoptotic cells and giant cells with condensed chromatin, and a deeply eosinophilic cytoplasm. The MLT and ADR treatments also significantly decreased the Ki-67 protein and vascular endothelial growth factor (VEGF) expression levels in the tumour masses. In conclusion, similar to ADR-treated tumour-bearing mice, MLT suppressed the growth and proliferation of tumour by inducing apoptosis and by inhibiting tumour vascularization. The current data recommend MLT as a safe natural chemotherapeutic adjuvant to overcome cancer progression after a clinical trial validates these results.

Voluntary alcohol consumption exacerbated high fat diet-induced cognitive deficits by NF-κB-calpain dependent apoptotic cell death in rat hippocampus: Ameliorative effect of melatonin

Modern sedentary lifestyle with altered dietary habits imposes the risk of human health towards several metabolic disorders such as obesity. The metabolic insults negatively affect the mental health status and quality life of affected individuals. Melatonin is a potent antioxidant with anti-inflammatory and neuroprotective properties. The aim of the present study was to investigate the protective effect of melatonin on the cognitive and neurochemical deficits induced by the high-fat diet (HFD) and alcohol (ALC) alone or in combination (HFD + ALC) in rats. Male Wistar rats were given ALC (3-15% i.e. increased gradually) and HFD for 12 weeks in different experimental groups. After 12 weeks, we found that simultaneous consumption of HFD and ALC exacerbates cognitive dysfunction and neurochemical anomalies. However, melatonin (10 mg/kg/day, i.p.) treatment for four weeks significantly prevented memory deficits, oxidative stress and neuroinflammation in HFD, ALC and HFD + ALC groups. RT-PCR analysis showed down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase-1 (HO-1) in ALC and HFD + ALC groups. Moreover, caspase-3 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) mRNA expression level were found up-regulated in hippocampus of HFD, ALC and HFD + ALC groups. However, calpain expression was found up-regulated only in the hippocampus of HFD + ALC group. Chronic treatment with melatonin significantly restored the aberrant gene expression level in HFD, ALC and HFD + ALC group. In conclusion, our findings indicated that melatonin can mitigate the HFD and ALC-induced cognitive deficits via attenuation of oxidative stress and calpain-1 dependent as well as independent caspase-3 mediated neuronal cell death.

Melatonin Attenuates 2,4-Dichlorophenoxyacetic Acid Toxicity in Kidney of Mice

Protective effects of melatonin against 2,4-Dichlorophenoxyacetic acid (2,4-D) induced nephrotoxicity in adult albino male mice of Swiss strain were evaluated in the present study. Twenty adult male albino mice were assigned into four groups with five mice in each group. Group I served as control; Group II - melatonin alone (10 mg/kg body weight); Group III - 2,4-D alone (50 mg/kg body weight) and Group IV - 2,4-D + melatonin was given orally for 45 days. Ameliorative effects of melatonin against oxidative stress of 2,4-D were evaluated by estimation of total protein, malondialdehyde (MDA), Total Glutathione (GSH) and Total Ascorbic Acid (TAA) level as well as Superoxide Dismutase (SOD) and Catalase (CAT) activity parameters. Effect of melatonin and 2,4-D alone and in combination on energy metabolism were also studied by assessment of succinate dehydrogenase (SDH), adenosine triphosphatase (ATPase), Acid Phosphatase (ACP) and Alkaline Phosphatase (ALP) activity. Along with this, the marker for kidney function i.e. creatinine was also evaluated in all studied groups. The significant value was considered at p<0.05. Significant reduction in levels of total protein, GSH, and TAA whereas an increase in MDA and creatinine levels were observed after 2,4-D treatment. Moreover, there was a decrease in the activity of SOD, CAT, SDH, ATPase, ACP, and ALP due to the herbicide treatment. These values were comparable to control when melatonin was given alone and in combination with 2,4-D. The study demonstrated nephroprotective potential of melatonin against oxidative stress and altered energy metabolism due to the toxicity of 2,4-D.