International Journal of

Toxicological and Pharmacological Research

e-ISSN: 0975 5160

p-ISSN: 2820-2651

Peer Review Journal

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Although preliminary results from some pilot studies were promising, longer-term studies in large numbers of patients were disappointing and none of the three macrolides decreased ischaemic events or provided clinical benefit; indeed, in one study an unexpected increase in cardiovascular mortality was seen in those taking clarithromycin. They can also help you find financial assistance for prescription medications or other healthcare costs based in your local area. the position of general counsel from until During this time, the global compliance concept and a corresponding organization was established.

1. Increase in Bax/Bcl-2 Ratio Induced by Salvigenin Through Mitochondria in Sw948 and HT-29 Human Colon Cancer Cell Line
Sarvestani N N, Sepehri H
Constituting an untold diversity of chemical structures makes natural products a valuable source of lead compounds in drug discovery. Multiple pharmacological studies, have led to the observations that polyphenolic antioxidants, such as flavonoids, acquire great therapeutic potential in battle against cancer. This study reports the anticancer effect of salvigenin against HT-29 and SW948 human colon cancer cell line through induction of apoptosis with no significant effect on normal HFFF-2 cell line. This natural polyphenolic compound, salvigenin, is an active ingredient of Salvia lachnocalyx and Salvia hydrangea. In this study, it has been shown the ability of salvigenin in induction of Bax/Bcl-2 ratio which lead to initiating apoptosis on human colon cancer cell line. Moreover, we have screened the increase in mitochondrial membrane potential on colon cancer cells treated by salvigenin. Bcl-2 family proteins and mitochondrial dysfunction are probably key regulators of the apoptotic response. Hence, salvigenin trigger one of the important pathways of anticancer feature of natural product. Dual effects of flavonoids, as an antioxidant or pro-oxidant, gives them this capacity to induce cell death from different way. Here it had shown that salvigenin increase ROS production in colon cancer cell line to accelerate cell death.

2. Acute Oral Toxicity of Lansioside D in Mice
Paula Angela N. Marfori, Ma. Dalisay G. Maligalig, Ma. Amelita C. Estacio, Rohani B. Cena, Mark Joseph M. Desamero, Mary Jasmine C. Ang, Eufrocinio C. Marfori
Lansioside D is a novel antimicrobial compound isolated from the peel of Lansium domesticum. This compound has a very remarkable activity against Gram-positive bacteria including Methicillin-resistant Staphylococcus aureus (MRSA). For the initial phase towards its development as a potential drug, a study to determine its acute oral toxicity was conducted. Forty male and 40 female ICR mice were equally distributed into three treatment groups and one control group. The treatment groups were administered with Lansioside D at various dose levels: 31.25 mg/kg body weight (low dose), 500 mg/kg body weight (middle dose) and 1000 mg/kg body weight (high dose). The control group was administered only with distilled water. Mortality within a 24-h period, as well as daily monitoring of food intake, water intake and body weight 14 days after the administration of the compound was done. Creatinine, urea nitrogen (BUN) and alanine aminotransferase (ALT) levels were also determined prior to treatment (day 0), on day 7 and on day 14. At the end of the 14-day observation period, animals were sacrificed and dissected. The stomach, kidneys and liver were isolated, their gross morphology and relative organ weights were determined, and thereafter subjected to histological evaluation. Results showed no mortalities after 24 h and no differences in all daily observed physiological parameters. Blood creatinine, BUN and ALT levels were normal prior up until the end of the experimentation. No differences were observed in the gross morphology of the stomach, kidneys and liver, as well as the relative organ weights among all the treatment and control groups. Histological examination of these organs revealed no significant abnormal findings. The above results suggest that Lansioside D is not toxic to mice and therefore has a potential to be developed as a new antibiotic.

3. Protective Role of Apigenin Against Rotenone Induced Model of Parkinson’s Disease: Behavioral Study
Chandran Anusha, Thangarajan Sumathi
Rotenone is a pesticide that has been shown to cause degeneration of dopaminergic neurons within the substantianigra and striatum. In this study, we investigated the protective effects of Apigenin on rotenone induced dopaminergic neurotoxicity. Adult male wistar albino rats were injected with rotenone (6μg/1μl in DMSO) or vehicle (1μl DMSO) into the right substantianigra pars compacta (SNpc) under stereotaxic surgery. Two varying doses of Apigenin (10 mg/kg and 20 mg/kg/ day, i.p.) were administered for 14 days. The significant increase in catalepsy, postural instability, impaired motor coordination, decrease in locomotor activity, and the decrease in rearing behavior caused due to rotenone induction was attenuated by treatment with varying doses of apigenin. These results suggest that apigenin may serve as a promising therapeutic tool in Parkinson’s disease.

4. Neurotoxic Effects of Gestational Exposure of Methyl Mercury on Different Brain Regions of F1 Generation; Neurobehavioural, Biochemical and Histological Study During Weaning Period of Rat.
Sherin J, Sumathi T
MeHg is an environmental neurotoxin. Exposure to MeHg during gestation causes cognitive and motor imbalance in the rat pups.  No studies are available on the differential effect of transplacental MeHg exposure on oxidative stress responses and cellular architecture in the specific motor and cognitive centers of rat offspring. Hence our study aimed to evaluate the changes in oxidative stress markers and histology in cerebral cortex, cerebellum and hippocampus of F1 generation due to prenatal MeHg exposure. We have tried four different doses viz, 0.5, 1.5, 2.5 and 3.5 mg/kg of MeHg in drinking water to the pregnant rats from GD 5 till parturition. Pups of 2.5mg/kg and 3.5 mg/kg group were not survived. In 0.5 and 1.5 mg/kg MeHg dosage group, on PND 21, the pups showed neurobehavioural toxicity in morris water maze, forced swim, rotarod, hotplate and open field behaviour tests. Increased TBARS levels and decreased GSH, GPx, Catalase and SOD were found in cerebral cortex, cerebellum and hippocampus. Appearance of gliosis and extensive neuronal degeneration in both 0.5mg/kg and 1.5mg/kg doses were observed. Among the doses, oxidative, histological and behavioural changes were significant in 1.5mg/kg group. Hence we conclude that developmental exposure of MeHg causes oxidative stress changes and histological damages in the cerebral cortex, cerebellum and hippocampus of neonatal brain around weaning period (PND 21) and is manifested as postnatal neurobehavioural impairment. Further molecular studies are needed in each brain regions to explore therapeutic targets of MeHg neurotoxicity in future.

5. Indiscriminate Use of Proton Pump Inhibitors and Possible Cardiovascular Risk
Tatyasaheb patil, Snehal Patil, Anuprita Patil, Shreedevi Patil
We have witnessed rise in the indiscriminate use of over the counter preparations of Proton pump inhibitors. Proton pump inhibitors are known to cause nutritional deficiencies, rebound acid hypersecretion and achlorhydria, acute interstitial nephritis, gastric carcinoid tumour.  Similarly, co-prescription with clopidogrel leads to various cardiovascular effects even among normal individuals. Though PPI may increase the risk of arrhythmias and enhance cardiovascular risk on high dose parenteral use of PPI, the role of PPI in modifying NO activity will definitely enhance the risk of cardiovascular events manifold among the general population. Hence, there is a definitive need to conduct cross sectional, prospective and community based trials to uncover the human applicability of the observation by these researchers and increase the pharmacovigilance for these class of drugs.

6. Therapeutic Effect of Olmesartan Medoxomile Alone and in Combination with Sulfasalazine in Experimentally Ulcerative Colitis Model in Rats
Darwish Fatima, Al laham Shaza
Background: Ulcerative colitis is a chronically recurrent inflammatory bowel disease of unknown origin. There is, as yet, no cure for this condition (other than colectomy in ulcerative colitis). Accumulating evidence has indicated the implication of angiotensinⅡ in the pathogenesis of inflammatory bowel diseases (IBD) via its proinflammatory features. The present study aimed to investigate the potential therapeutic effects of Omesartan Medoxomil (OLM-M) alone and in combination with sulfasalazine (SZ) on acetic acid induced- ulcerative colitis in rats. Methods: A total of 35 male wistar rats were included in the study. Animals were divided into 5 groups (n = 7): group (normal control group), groupⅡ (acetic acid group), groupⅢ (acetic acid+Sulfasalazine 360 mg/kg p.o used as reference), groupⅣ (acetic acid+ Omesartan medoxomil 5 mg/kg p.o), groupⅤ (acetic acid+Sulfasalazine 360 mg/kg+ Olmesartan medoxomil 3  mg/kg p.o). Rats received treatment for seven consecutive days after induction of colitis by intra-rectal acetic acid (2ml 4% v/v) administration. Rats were sacrificed under ether anesthesia for assessment of the colonic mucosal injury using body weight loss, colon weight / length ratio, macroscopic damage, histological study, as well as by biochemical measurement of reduced glutathione (GSH). Results: Our results showed that SZ, OLM-M and their combination decreased body weight loss, weight/length ratio, macroscopic and microscopic colonic damage scores caused by administration of acetic acid. Also significantly increased the levels of glutathione compared to acetic acid-induced colitis group. Conclusion: The results suggested that intracolonic instillation of acetic acid produced acute colitis. Both SZ and OLM-M exerted anti-inflammatory and antioxidant effects on acetic-acid-induced colitis. In addition, OLM-M potentiated the anti-inflammatory and antioxidant effect of SZ.

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