Abstract

Hamid Didi68238* and Made Eko68239

Vitamin A and Vitamin D play an important role in immunity. The purpose of this study is to analyze whether vitamin D3 and retinyl palmitate could induce the effectiveness of 2^nd line Anti-Tuberculosis (TB) drugs. We majorly focus on cell death process. C3HeB/FeJ mice were infected with Multidrug-Resistant (MDR) strain Mycobacterium tuberculosis and grouped randomly. The 1^st group was euthanized to evaluate TB germs grown in the lungs. 2^nd group is received no therapy. The 3^rd group was given 2^nd line anti-TB drugs. The 4th was given retinyl palmitate along with 2^nd line drugs. 5th group was given 2^nd line drugs with D3. 6th group was given a combination of 2^nd line drugs, retinyl palmitate and D3. Immunohistochemistry demonstrated the quantitative measurement of nuclear receptor expression of Vitamin D (VDR) and Vitamin A (Retinoic Acid Receptor Gamma 2) (RARγ2), apoptosis Caspase-3 (CASP3) marker, autophagy markers Cathelin-Related Antimicrobial Peptide (CRAMP) and Microtubule-Associated Protein 1 Light Chain 3B (MAP1LC3B), marker of necrosis namely, Receptor Interacting threonine Kinase 3 (RIPK3) and interstitial collagenase Matrix Metalloproteinase 1 (MMP1). TB germs in lung were counted in Colony Forming Units (CFU). Partial Least Square Structural Equation Modeling (PLS-SEM) with SmartPLS 3.2.6 software was used to analyze structural model within variable. Vitamin D3 plays an important role in increasing autophagy of infected cells and MMP1. Both vitamin D3 and retinyl palmitate played a role in increasing Casp3 expression and reducing CFU. The combination of D3 and retinyl palmitate reduced cell necrosis which was characterized by a decrease in RIPK3. Our study proves that the combination of D3 and retinyl palmitate supplementation on the 2^nd line anti-TB drugs reduces cell necrosis directly.