Comparative evaluation of some flavonoids and tocopherol acetate against the systemic toxicity induced by sulphur mustard

Abstract

Objective: To evaluate the protective value of quercetin, gossypin, Hippophae rhamnoides (HR) flavone and tocopherol acetate against the systemic toxicity of percutaneously administered sulphur mustard (SM) in mice.

Materials and methods: Quercetin, gossypin, HR flavone or tocopherol acetate (200 mg/kg, i.p.) were administered just before percutaneous administration of SM and protection against the SM lethality was evaluated. In another experiment quercetin, gossypin, HR flavone or tocopherol acetate were administered against 2 LD(50) SM. The animals were sacrificed seven days post SM administration and various biochemical parameters were estimated.

Results: The protection against the lethality of SM was very good with the flavonoids (quercetin = 4.7 folds; gossypin = 6.7 folds and HR flavone = 5.6 folds), compared to no protection with tocopherol acetate (0.7 fold). SM (2 LD(50)) showed decrease in reduced and oxidised glutathione (GSH and GSSG) levels, and an increase in malondialdehyde level (MDA). Oxidative stress enzymes like glutathione peroxidase, glutathione reductase and superoxide dismutase were significantly decreased. The total antioxidant status was also significantly decreased. Additionally, there was a significant increase in red blood corpuscles and hemoglobin content. All the flavonoids significantly protected the GSH, GSSG and MDA, and also the hematological variables. Tocopherol acetate failed to offer any protection in those parameters. Gossypin protected glutathione peroxidase, while HR flavone protected both glutathione reductase and glutathione peroxidase significantly. The decrease in body weight induced by SM and the histological lesions in liver and spleen were also significantly protected by the flavonoids but not by tocopherol acetate.

Conclusion: The present study supports that SM induces oxidative stress and flavonoids are promising cytoprotectants against this toxic effect.

Keywords: Gossypin; Hippophae rhamnoides flavone; oxidative stress; quercetin; sulphur mustard.

Figure 1

Effect of flavonoids in comparison to tocopherol acetate (200 mg/kg, i.p.) against percutaneously administered SM (2 LD50). Q = quercetin; G = gossypin; HR = H. rhamnoides flavone; TA = tocopherol acetate. Mean ± SE (n = 4); Flavonoids and tocopherol acetate were administered simultaneously with SM. The animals were sacrificed seven days post SM administration. a - Significantly different from control group; b - Significantly different from SM group. Control values: [Table: see text]

Figure 2

Effect of flavonoids in comparison to tocopherol acetate (200 mg/kg, i.p.) against percutaneously administered SM (2 LD50) on mice liver. Flavonoids and tocopherol acetate were administered simultaneously with SM. The animals were sacrificed seven days post SM administration. Q = quercetin; G = gossypin; HR = H. rhamnoides flavone; TA = tocopherol acetate. H&E, ×100.

1. Control liver showing normal hepatic parenchyma, hepatic lobules and hepatocytes,

2. SM administered mice liver (2 LD50) showing granulovacuolar degeneration and perinuclear clumping of cytoplasm,

3. Quercetin administration with SM, showing reduced hepatic lesions,

4. Gossypin administration with SM showing lesser magnitude of hepatic lesions,

5. HR-flavone administration with SM showing protection of hepatic degeneration,

6. Tocopherol acetate administration with SM showing marginal protection.

Figure 3

Effect of flavonoids in comparison to tocopherol acetate (200 mg/kg, i.p.) against percutaneously administered SM (2 LD50) on mice spleen. Flavonoids and tocopherol acetate were administered simultaneously with SM. The animals were sacrificed seven days post SM administration. Q = quercetin; G = gossypin; HR = H. rhamnoides flavone; TA = tocopherol acetate. H&E, ×100.

1. Control spleen showing normal splenic parenchyma germinal centre, red and white pulp,

2. SM administered mice spleen (2 LD50) showing congestion, hypocellularity and parenchymal degeneration,

3. Quercetin administration with SM showing protection with lesser hypocellularity,

4. Gossypin administration with SM showing lesser magnitude of splenic degeneration,

5. HR-flavone administration with SM showing minimal lesions,

6. Tocopherol acetate administration with SM showing marginal protection.