Hesperetin alleviates DMH induced toxicity via suppressing oxidative stress and inflammation in the colon of Wistar rats.

1,2-Dimethylhydrazine (DMH), a colon-specific environmental toxicant is one among the carcinogen responsible for the cause of colon cancer. The present study was designed to evaluate the protective effect of Hesperetin (HST) against colon toxicity induced by DMH in Wistar rats. HST, a flavonoid widely found in citrus fruits possesses several biological activities including anti-microbial, anti-oxidant properties among others. A single dose of DMH (40 mg/kg body weight) was administered subcutaneously on 1st day for induction of colon toxicity followed by oral treatment with HST at a dose of 20 mg/kg bodyweight for 14 consecutive days. DMH administration leads to excessive ROS generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Our result showed HST significantly ameliorates DMH-induced lipid peroxidation and also substantially increases the activity/level of various anti-oxidant proteins (GR, GPx, GST, GSH, and SOD). HST was also found to reduce the expression of inflammatory proteins (TNF-α, IL-6, i-NOS, COX-2, NF-kB-p65), goblet cell disintegration as well as mucin depletion (sulfo and sialomucin) in the colon that was found to be elevated upon administration of DMH. Our histological results further provide confirmation of the protective role of HST against DMH-induced pathological alterations. The results of the present study demonstrate supplementation of HST is beneficial in ameliorating DMH-induced toxicity by suppressing oxidative stress, inflammation, goblet cell disintegration as well mucin depletion in the colon of Wistar rats.

The fabrication and assessment of mosquito repellent cream for outdoor protection.

Mosquito-borne infections like dengue, malaria, chikungunya, etc. are a nuisance and can cause profound discomfort to people. Due to the objectional side effects and toxicity associated with synthetic pyrethroids, N,N-diethyl-3-methylbenzamide (DEET), N,N-diethyl phenylacetamide (DEPA), and N,N-di ethyl benzamide (DEBA) based mosquito repellent products, we developed an essential oil (EO) based mosquito repellent cream (EO-MRC) using clove, citronella and lemongrass oil. Subsequently, a formulation characterization, bio-efficacy, and safety study of EO-MRC were carried out. Expression of Anti-OBP2A and TRPV1 proteins on mosquito head parts were studied by western blotting. In-silico screening was also conducted for the specific proteins. An FT-IR study confirmed the chemical compatibility of the EOs and excipients used in EO-MRC. The thermal behaviour of the best EOs and their mixture was characterized by thermogravimetric analysis (TGA). GC-MS examination revealed various chemical components present in EOs. Efficacy of EO-MRC was correlated with 12% N,N-diethyl benzamide (DEBA) based marketed cream (DBMC). Complete protection time (CPT) of EO-MRC was determined as 228 min. Cytotoxicity study on L-132 cell line confirmed the non-toxic nature of EO-MRC upon inhalation. Acute dermal irritation study, acute dermal dose toxicity study, and acute eye irritation study revealed the non-toxic nature of EO-MRC. Non-target toxicity study on Danio rerio confirmed EO-MRC as safer for aquatic non-target animals. A decrease in the concentration of acetylcholinesterase (AChE) was observed in transfluthrin (TNSF) exposed Wistar rats. While EO-MRC did not alter the AChE concentrations in the exposed animals. Results from western blotting confirmed that Anti-OBP2A and TRPV1 proteins were inhibited in TNSF exposed mosquitoes. Mosquitoes exposed to EO-MRC showed a similar expression pattern for Anti-OBP2A and TRPV1 as the control group. In silico study revealed eight identified compounds of the EOs play significant roles in the overall repellency property of the developed product. The study emphasizes the mosquito repellent activity of EO-MRC, which could be an effective, eco-friendly, and safer alternative to the existing synthetic repellents for personal protection against mosquitoes during field conditions.

Quercetin ameliorates reactive oxygen species generation, inflammation, mucus depletion, goblet disintegration, and tumor multiplicity in colon cancer: Probable role of adenomatous polyposis coli, ß-catenin.

1,2 Dimethyl hydrazine (DMH), a cogent environmental toxicant, targets the colon. Previous reports suggest that DMH-mediated dysregulation of the Wnt/ß-catenin pathway plays a vital role in the initial events of colon carcinogenesis. Our study was designed to investigate the effect of quercetin on DMH-mediated colon cancer by targeting adenomatous polyposis coli (APC) and ß-catenin in Wistar rats. Animals were pretreated orally with quercetin at doses of either 25 or 50 mg/kg bodyweight (bw) and DMH at a dose of 20 mg/kg bw subcutaneously up to the 15th week and sacrificed after the 30th week. DMH administration leads to reactive oxygen species generation, resulting in an imbalance in redox homeostasis and causing membrane lipid peroxidation, which is also partly due to the decrease in the level of tissue antioxidant machinery. Increased inflammatory and proliferative proteins were observed in DMH-induced colon cancerous rats. DMH treatment also led to dysregulation in the apoptotic pathway with decreased Bax:Bcl-2 ratio. Quercetin pretreatment ameliorates DMH-induced proliferation, activities of detoxifying enzymes, and putative early markers (mucin depletion and goblet cell disintegration) in colonic tissue. It also significantly regulates APC and ß-catenin expression and inhibits tumor incidence and multiplicity. Histological results further confirm the beneficial role of quercetin in averting DMH-induced pathological alterations.

Safety profile of silver sulfadiazine-bFGF-loaded hydrogel for partial thickness burn wounds.

In the present investigation, the safety of novel combinational silver sulfadiazine-bFGF-loaded hydrogel was assured by performing acute skin irritation, sensitization, acute dermal toxicity, and eye irritation in compliance with the Organization for Economic Co-operation and Development guidelines. In the skin irritation study, placebo, test, and positive control (0.8% w/v aqueous solution of formaldehyde) were applied on New Zealand rabbits and monitored for abnormal skin responses including erythema and edema. The placebo and test formulation did not induce any adverse reactions and were classified as nonirritating materials. In the skin sensitization test, guinea pigs were sensitized by positive control (0.1% w/v 1-chloro-2,4-dinitrobenzene in 10% of propylene glycol as a standard skin sensitizing agent), placebo, and test formulations. Weak sensitization was observed in the placebo and test formulation treated groups. Additionally, acute dermal toxicity test was performed in Wistar rats, where no signs of toxicity were observed in biochemical, hematological, and histopathological studies. Moreover, the acute eye irritation test was carried out in rabbits and no abnormal clinical signs were evident in the cornea or iris. As a whole, these findings suggest that the hydrogel formulation does not cause any skin irritation, skin sensitizationand dermal toxic effects, and eye irritation following dermal and ocular applications, respectively. Therefore, all the findings obtained from this preclinical study indicated that this hydrogel formulation is nontoxic and safe for use in animal models.

Colono-protective Potentiality of Methanolic Bark Extract of Acacia catechu: A Medicinal Plant against 1,2-Dimethylhydrazine-Induced Toxicity in Wistar Rats.

The protective efficacy of methanolic bark extract of Acacia catechu Willd. (MEBA) against 1,2-dimethylhydrazine (DMH)-induced colon toxicity was investigated. Acacia catechu is considered one of the most potent medicines for various diseases in Ayurveda, a traditional system of Indian medicine. It is a widely used herb that contains a variety of bioactive components such as phenolic acids, alkaloids, and flavonoids among others. In the present study, MEBA was used as a pretreatment orally at two doses (250 and 500 mg/kg body weight [b.w.] once daily for 7 days), and DMH was administered (at a dose of 40 mg/kg b.w.) subcutaneously on day 7 in Wistar rats. The protective potential of MEBA was assessed in terms of the activity of antioxidant enzymes, lipid peroxidation, and expression of inflammatory markers (iNOS, COX-2, NF-κB, IL-6). Pretreatment with MEBA significantly abrogated oxidative damage by diminishing tissue lipid peroxidation, increasing enzymatic activities of various antioxidant enzymes (catalase, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, reduced glutathione), and diminishing the induced expression of inflammatory markers in the colon tissue of Wistar rats. Furthermore, histopathological findings revealed that pretreatment with (MEBA) reduced intense filtration of inflammatory cells and significantly restored the architecture of colonic tissue. The results of this study indicate that MEBA significantly suppresses DMH-induced toxicity by ameliorating oxidative stress and inflammation and by restoring the architecture of colon tissue.