INFLUENCE OF ZINCOVIT DROP (NUTRITIONAL FOOD SUPPLEMENT) ON IMMUNE SYSTEM IN NORMAL AND CYCLOPHOSPHAMIDE INTOXICATED WISTAR RATS

ABSTRACTObjective: The aim of the present study was to investigate the influence of Zincovit (ZVT) drop (nutritional food supplement) on the immune systemin normal healthy and cyclophosphamide (CP) intoxicated Wistar rats.Methods: The study was carried out in healthy and immunotoxic Wistar rats (CP; 20 mg/kg/day) with ZVT drop (a combined formulation ofmultivitamin-multimineral, flaxseed oil, and lysine) at the dose of 25 and 50 mg/kg/day for 45 days. Hematological and immunological parameters,such as immunoglobulin (Ig)G, IgM, interferon-γ, interleukin-2, and interleukin-4, were assessed. In addition, histopathological examination of thespleen was also performed.Results: There were no significant changes in all the hematological parameters such as total leukocyte, differential leukocyte, total erythrocyte, andtotal platelets count, hemoglobin amount and also the immunological parameters such as IgG, IgM, interferon-γ, and interleukin-4 level among thetreatment groups except interleukin-2. There was a significant increase in interleukin-2 level in the group of animals treated with ZVT drop at the doseof 25 mg/kg (p<0.001) and 50 mg/kg (p<0.05) in comparison with normal control animals.Conclusion: The present study revealed the immunomodulatory effect of ZVT drop at the dose of 25 and 50 mg/kg/day in normal healthy Wistar rats.Keywords: Zincovit drop, Flax seed oil, Multivitamin-multimineral nutritional food supplement, Cyclophosphamide, Immunomodulatory

CORRELATION OF GENDER AND LEPTIN WITH ANALGESIC EFFECT OF TRAMADOL IN RATS

 Objective: The objective of the study was to investigate the correlation of gender and serum leptin level with analgesic modulation of tramadol in Wistar rats.Methods: A total of 48 Wistar rats (body weight 100–150 g), 24 each male and female Wistar rats were randomly divided into two groups (n=6/group) (Group I - Control- 0.9% NaCl; 1 ml/kg/day i.p. and Group II - Tramadol 10 mg/kg/day i.p.) for each nociception model - plantar test and acetic acid induced writhing test. The treatment duration was of 5 days. Paw withdrawal latency (PWL) was assessed using plantar test and writhing movements were observed following administration of 0.8% acetic acid; 10 ml/kg i.p.Results: PWL was significantly decreased (p<0.001) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in female control group compared to male control group. In tramadol treated female rats, PWL was significantly decreased (p=0.005) and both number of writhing movements and serum leptin concentrations were significantly increased (p<0.001) in comparison with the tramadol treated male rats. PWL was negatively correlated with serum leptin concentration (Pearson correlation coefficient= −0.826, two-tailed significance= 0.000), and writhing movements were positively correlated with serum leptin concentration (Pearson correlation coefficient= 0.505, two-tailed significance= 0.012).Conclusions: The present study revealed that female rats have more serum leptin concentration than male rats which could be one of the possible reasons for having more pain sensitivity to noxious stimuli in female rats compared to male rats. Tramadol treatment at the dose of 10 mg/kg for 5 days has decreased serum leptin level in rats which might be one of the additional mechanisms of tramadol to reduce pain

EVALUATION OF BURN WOUND HEALING ACTIVITY OF TOPICAL REGULAR INSULIN IN NON-DIABETIC AND STREPTOZOCIN-INDUCED DIABETIC RATS

Objective: The role of insulin in the regulation of energy metabolism, protein synthesis, cell differentiation and growth suggests that this hormone could also play an essential role in regulation of wound healing. Consequently, the aim of the present study was to investigate the effects of topical insulin administration on burn wound healing in both non-diabetic and streptozocin-induced diabetic Wistar rats. Methods: Wound healing activity was assessed by burn-wound model. This study was conducted using six groups of Wistar strain adult rats of either sex (n = 6). First three groups were non-diabetic (ND) rats and the other three had diabetic (D) rats: (i) ND control (sterile water); (ii) ND standard (silver sulfadiazine cream); (iii) ND test (topical Insulin); (iv) D control (sterile water); (v) D standard (silver sulfadiazine cream); (vi) D test (topical insulin). Wound healing was assessed by wound contraction rate and complete epithelialization time. Results: There was significant (p<0.05) delay in wound healing in diabetic rats when compared to normal rats. It was found that topical insulin administration enhanced burn wound healing by shortening the time needed for complete epithelialization in the non-diabetic and diabetic group. Conclusion: This study revealed that topical insulin application to partial thickness burn wounds accelerates wound healing in rats with or without acute diabetes

INFLUENCE OF GENDER AND OBESITY ON ANALGESIC MODULATION OF TRAMADOL IN RATS

Objective: The objective of this study was to investigate the influence of gender and obesity on analgesic modulation of tramadol in Wistar rats.Methods: This study was carried out in two sets of experiments. In Set I experiment - 48 rats (body weight ≤150 g), 24 each male and female rats were randomly divided into two groups (n=6/group) (Group I - Control; 0.9% NaCl; 1 ml/kg/day i.p. and Group II - Tramadol 10 mg/kg/day i.p.) for each nociception model - plantar test and acetic acid-induced writhing test. The treatment duration was of 5 days. On the last day of treatment (i.e., on the 5th day), paw withdrawal latency (PWL) was assessed using plantar test, and writhing movements were observed following administration of 0.8% acetic acid; 10 ml/kg i.p. Set II experiment was repeated like Set I experiment among rest 48 high-fat diet-fed rats (body weight ≥300 g).Results: For both males and females, PWL was significantly decreased (p<0.05) in obese control groups compared to lean control groups. A number of writhing movements were significantly increased (p<0.01 for males and p<0.001 for females) in obese control groups compared to lean control groups. In tramadol-treated obese rats, PWL was significantly decreased (p<0.01 for males and p<0.05 for females), and number of writhing movements were significantly increased (p<0.01 for both males and females) in comparison with the tramadol-treated lean rats.Conclusion: The present study revealed that obese female rats experience more pain sensation to noxious stimuli compared to lean male rats and also the analgesic effect of tramadol is more pronounced in lean male rats compared to obese female rats

INFLUENCE OF TOPICAL RETAPAMULIN (1%) OINTMENT, SOFINOX- RD CREAM, SOFINOX CREAM (2%), ZINC FUSIDATE CREAM (2%) AND ZINC FUSIDATE OINTMENT (2%) ON NASAL MUCOSAL SURFACE SAFETY IN NEW ZEALAND ALBINO RABBITS

Objective: To investigate the comparative safety of Retapamulin 1% ointment, Sodium fusidate 0.25%, Sofinox 2% cream, Zinc fusidate 2% cream and Zinc fusidate 2% ointment on nasal mucosal surface in rabbits.Methods: In the experiment a total of 30 adult New Zealand albino rabbits of either sex were used. The rabbits were divided into five groups of six rabbits each. A thin layer of the drug was applied in the right nostril and left nostril was kept as control (no treatment) to their corresponding treatment group. Nasal safety of these drugs was assessed with the help of a symptom scoring system and photographic observations.Results: There was significant decrease of nasal rubbing (Rhinocnesmus) behaviors in experimental animals of Sofinox RD cream (p<0.001), Sofinox 2% cream (p<0.001), Zinc fusidate cream (p<0.001) and Zinc fusidate ointment (p<0.001) treated groups when compared with Retapamulin 1% ointment treated group. More redness was observed in nasal mucosal surface of both nostrils (Right nostril- Retapamulin 1% ointment, Left nostril- Control) of Retapamulin group animals in comparison with Sofinox RD cream, Sofinox 2% cream, Zinc fusidate 2% cream and Zinc fusidate 2% ointment group animals.Conclusion: In the present study, the comparative safety of test drugs on nasal mucosal surface of rabbits were found as- Zinc fusidate ointment > Zinc fusidate cream > Sofinox RD cream ~ Sofinox 2% cream > Retapamulin 1% ointment. Further, clinical evaluation has to be performed to precisely define the safety of Zinc fusidate ointment, Zinc fusidate cream, Sofinox RD cream and Sofinox 2% cream on nasal mucosal surface of human subjects.Â

EFFECT OF FUCITHALMIC AND SOFINOX EYE DROPS ON EXPERIMENTAL ALLERGIC CONJUNCTIVITIS IN RATS

Objective: To investigate the therapeutic effect of Fucithalmic 1%, Sofinox 0.5% and 1% eye drops against an IgE-mediated allergic conjunctivitis model in Wistar rats. Methods: IgE-mediated allergic conjunctivitis was induced by ovalbumin antigen challenge. Allergic conjunctivitis induced control rats (Group I) received normal saline (0.9% NaCl; 10 µl/eye) whereas Fucithalmic 1% (Group II), Sofinox 0.5% (Group III) and 1% (Group IV) were administered as 10, 20 and 10 µl/eye respectively to the treatment group animals (n=6) for 15 days. Eye scratching behavior, hypothermia and edema was evaluated after topical antigen challenge. Results: Sofinox 1% eye drops (10 µl/eye) significantly attenuated eye scratching behavior, hyperemia and edema in comparison with allergic conjunctivitis induced control (p < 0.001) and Fucithalmic 1% treated rats (p < 0.05). Eye scratching behavior and edema was also significantly decreased in Sofinox 0.5% eye drops (20 µl/eye) treatment group as compared to allergic conjunctivitis induced control rats (p < 0.05). Conclusion: The present study revealed that the Sofinox eye drop is the potential agent that could offer a novel therapeutic opportunity against IgE-mediated allergic conjunctivitis in Wistar rats

Neuronutraceuticals Combating Neuroinflammaging: Molecular Insights and Translational Challenges—A Systematic Review

Neuropathologies, such as neuroinflammaging, have arisen as a serious concern for preserving the quality of life due to the global increase in neurodegenerative illnesses. Nowadays, neuronutraceuticals have gained remarkable attention. It is necessary to investigate the bioavailability, off-target effects, and mechanism of action of neuronutraceuticals. To comprehend the comprehensive impact on brain health, well-designed randomized controlled trials testing combinations of neuronutraceuticals are also necessary. Although there is a translational gap between basic and clinical research, the present knowledge of the molecular perspectives of neuroinflammaging and neuronutraceuticals may be able to slow down brain aging and to enhance cognitive performance. The present review also highlights the key emergent issues, such as regulatory and scientific concerns of neuronutraceuticals, including bioavailability, formulation, blood–brain permeability, safety, and efficacy

Methyl Gallate Attenuates Doxorubicin-Induced Cardiotoxicity in Rats by Suppressing Oxidative Stress

Doxorubicin-induced cardiotoxicity is the leading cause of morbidity and mortality among cancer survivors. The present study was aimed to investigate the cardioprotective potential of methyl gallate; an active polyphenolic nutraceutical, against doxorubicin-induced cardiotoxicity in Wistar rats. Twenty-four female Wistar rats (150–200 g) were divided into four groups (n = 6) which consist of normal control (group I), doxorubicin control (group II), test-A (group III), and test-B (group IV). Group III and group IV animals were prophylactically treated with methyl gallate 150 mg/kg/day and 300 mg/kg/day orally, respectively, for seven days. Doxorubicin (25 mg/kg; single dose) was administered through an intraperitoneal route to group II, III, and IV animals on the seventh day to induce acute cardiotoxicity. On the 8th day, besides ECG analysis, serum CK, CK-MB, LDH, AST, MDA, and GSH were assayed. Following gross examination of isolated hearts, histopathological evaluation was performed by light microscopy. A significant (p < 0.05) cardiac injury, as well as oxidative stress, was observed in doxorubicin control rats in comparison to normal control rats. Methyl gallate at both the doses significantly (p < 0.05) reduced doxorubicin-induced ECG changes, dyslipidaemia, and elevation of CK, CK-MB, LDH, AST, MDA and increased GSH level. Methyl gallate reversed the doxorubicin-induced histopathological changes in the heart. The present study revealed that methyl gallate exerts cardioprotection against doxorubicin-induced cardiotoxicity in female Wistar rats by suppressing oxidative stress. Our study opens the perspective to clinical studies for consideration of methyl gallate as a potential chemoprotectant nutraceutical in the combination chemotherapy with doxorubicin to limit its cardiotoxicity