To Study and Evaluate the Role of Gut Modulation on the Toxicity and Efficacy of Doxorubicin

Abstract

oxorubicin is one of the most effective chemotherapy drugs used against tumors in the treatment of several cancer types. Two different mechanisms (a) intercalation of doxorubicin into DNA and inhibition of topoisomerase II leading to changes in chromatin structure, (b) generation of free radicals and oxidative damage to biomolecules, have been proposed to explain the mode of action of this drug in cancer cells. Chemotherapeutic can further cause microbiome alterations that facilitate the emergence of antibiotic- resistant microorganisms and especially for pediatric patients, increase risk of dysbiosis- related health complication later in life (e.g., obesity, asthma, diabetes). Chemotherapeutic drugs are known to perturb the microbiome as well. Chitin is a polysaccharide obtained from crustaceans, fungus and insects that also is biocompatible and biodegradable. Chitosan is converted from chitin by deacetylation. Chitosan has been reported to have antioxidant, anticancer, anti-inflammatory, immunostimulant, wound healing cholesterol lowering, antibacterial and antifungal qualities, which can be used as an active component of the diet. Chitosan can be used as a prebiotic to boost the colonic mucosal populations of beneficial bacteria while suppressing pro inflammatory bacteria, hence reducing gut microbiota imbalance and mucosal inflammation. Our hypothesis is to check that how Doxorubicin is involved in Gut micro floral alteration and does the co-administration if gut modulators influence the efficacy of doxorubicin. We have treated animals parallelly by giving chemotherapeutic Drug Doxorubicin and Chitosan microspheres. We observed that there are chances to restore Doxorubicin caused Micro floral dysbiosis by giving gut modulators such as chitosan microspheres. Futher this study can be useful to reduce the toxicity in the intestine by lowering the doses of chemotherapeutic drug and parallelly giving chitosan microsphere as gut modulator to restore gut biota.