Anti-proliferative effects of the combination of Sulfamethoxazole and Quercetin via caspase3 and NFkB gene regulation: an in vitro and in vivo study.

Combination therapy comprising natural polyphenols and anticancer drugs has been used to decrease the adverse effects and increase the effectiveness and antioxidant activities of the drugs. The antioxidant and anticancer effects of quercetin (Q), a nutritive polyphenol, have been observed both in vitro and in vivo. Likewise, the anticancer activity of sulfamethoxazole (S) has been demonstrated in vitro and in vivo. This study aimed to investigate the in vitro and in vivo anticancer effects of Q alone and in combination with S. The in vitro effects of S, Q, and S + Q on HCT-116, HepG2, MCF-7, and PC3 cell lines were examined. Additionally, the in vivo effects of these drugs were evaluated using Ehrlich ascites carcinoma (EAC) tumor-bearing mice. The in vitro data revealed the potent anticancer activity of S + Q through the induction of apoptosis and cell cycle arrest. The EAC-inoculated mice treated with S + Q presented with elevated SOD, GSH, CAT, and TAC levels and decreased malondialdehyde levels compared with the untreated EAC group, thus revealing the antioxidant and protective actions of S + Q against EAC cell invasion. Furthermore, the downregulation of NFkB and upregulation of the caspase3 gene in the EAC-inoculated mice treated with the S + Q indicated the induction of the apoptotic pathway and decrease in both cell proliferation and metastasis. In conclusion, the combination of S and Q might exert anticancer effects by inducing apoptosis and exhibiting selective toxicity against the cancer cells and thereby protecting the vital organs.

Therapeutic potential of a novel combination of Curcumin with Sulfamethoxazole against carbon tetrachloride-induced acute liver injury in Swiss albino mice.

BACKGROUND: In the current study, we have investigated the effect of each of curcumin (CUR) and sulfamethoxazole (SMX) either separate or mixed together (CUR + SMX) on biochemical, hematological and histological alternations associated with carbon tetrachloride (CCl4)-induced liver fibrosis in mice. RESULTS: CCl4, caused changes of several biomarkers, proving its hepatotoxic effects, such as an increase in aminotransferases liver enzymes alanine and aspartate transaminases (ALT, AST), malondialdehyde (MDA), and nitric oxide (NO) formation, with a decrease in superoxide dismutase (SOD), glutathione reductase (GSSG), total antioxidant capacity (TAO), glutathione (GSH), total protein, and albumin, compared to a negative control mice group. Compared to the CCl4 group of mice, the CUR and SMX separate and/or together (CUR + SMX) treatments showed significance in (p < 0.001), ameliorated liver injury (characterized by an elevation of (ALT, AST) and a decrease (p < 0.001) in serum albumin and total protein), antioxidant (characterized by a decrease in (p < 0.001) MDA, NO; an increase (p < 0.001) SOD, GSSG, TAO; and reducing GSH), hematological changes (characterized by a decrease (p < 0.001) in white blood cells count and an increase (p < 0.001) in platelets count, hematocrit levels, hemoglobin concentration, and (p < 0.05) red blood cells count), SDS-PAGE electrophoresis with a decrease in protein synthesis and changes in histological examinations. CONCLUSIONS: CUR and SMX either separate or together (SUR + SMX) may be considered promising candidates in the prevention and treatment of liver fibrosis.

Neutralizing activity and safety of human monoclonal antibodies against hepatitis C virus.

AIM: Assessment of the neutralizing activity of human monoclonal antibodies against HCV and also study their safety in experimental small animals (Swiss mice). MATERIALS AND METHODS: Assessment of neutralizing activity of human monoclonal antibodies against HCV envelope regions (E1, E2) by two methods: by HCV cc infectious system 1) and by using positive HCV positive serum as source of HCV particles genotype 4a (neutralizing assay 2). Dot ELISA was used to study the activity of the generated antibodies. Safety and toxicity of the generated human antibodies were tested by assessing the changes in the biochemistry of liver function and kidney function tests, Complete blood counts (CBC) and studying the pathological changes with different concentrations of purified human antibodies were carried out.. RESULTS: Human Abs # 5 & 11 showed neutralizing activity by (neutralizing assay 2) but were not neutralizing by HCV cc assay. Human Abs # 12 & 15 showed neutralizing activity by the two methods i.e our generated human antibodies Abs# 5 &11 & 12 & 15 were neutralizing for HCV genotype 4a and Abs # 12 & 15 were neutralizing for HCV genotypes 4a and 2a. Liver and kidney functions and CBC results indicated that doses of 10 µg, 100 µg were safe. The histopathological results indicated that the dose of 10 µg of purified human monoclonal antibodies per mouse body weight was safe. CONCLUSION: The generated human monoclonal antibodies can be used to develop potent immunotherapy agents that can be administrated for the post-transplantation patients to prevent the recurrence of HCV infection. Also, the monoclonal antibodies can be used to develop a candidate vaccine against HCV.

Mice Antibody Response to Conserved Nonadjuvanted Multiple Antigenic Peptides Derived from E1/E2 Regions of Hepatitis C Virus.

Synthetic peptides are one of the hepatitis C virus (HCV)-specific small molecules that have antiviral activity and represent a target for HCV vaccine. This study aims to determine the lowest concentration of adjuvanted and non-adjuvanted (multiple antigenic peptide [MAP]) form of three conserved HCV envelope peptides that can induce murine immunogenic responses and evaluate the neutralization capacities of the generated antibodies (Abs) against HCV in cultured Huh7.5 cells. In this study, three HCV synthetic peptides, E1 peptide (a.a 315-323) and E2 peptides (a.a 412-419 and a.a 516-531) were synthesized. Female Balb/c mice were immunized with different concentration of either adjuvanted linear peptides or nonadjuvanted MAP peptides to determine the lowest dose that generates Ab responses enough to confer viral neutralization in vitro. The humoral responses targeting these peptides in immunized mice sera were measured by enzyme-linked immunosorbent assay (ELISA). Viral neutralization capacities of the generated mice Abs were assessed using Huh7.5 cells infected with the HCVcc infectious system (J6/JFH-1). The results of this study showed that the MAPs induce higher Ab titers than adjuvanted linear peptides after 4 weeks of immunization (p = 0.003). The viral neutralization experiments showed that the immunized mice sera contain anti E1/E2 Abs that blocked HCVcc (J6/JFH-1) entry into Huh7.5 cells. In conclusion, the three HCV envelope MAP peptides are more immunogenic and produce higher neutralizing Abs than linear peptides; therefore, they can be essential components for HCV vaccine.