A 90 day chronic toxicity study of Nigerian herbal preparation DAS-77 in rats

Abstract

Background: The herbal preparation DAS-77, used for the treatment of various ailments in Nigeria, contains the milled bark of Mangifera indica L. and root of Carica papaya L. Toxicological assessment of the preparation was carried out in this study.

Methods: In the acute toxicity study, DAS-77 was administered to mice p.o. up to 20 g/kg in divided doses and i.p. at 250-3000 mg/kg. Mortality within 24 h was recorded. In the chronic toxicity study, rats were treated p.o. for 90 days at doses of 80, 400 (therapeutic dose, TD) and 2000 mg/kg. By 90 days, animals were sacrificed and blood samples collected for hematological and biochemical analysis. Organs were harvested for weight determination, antioxidants and histopathological assessments.

Results: DAS-77 did not produce any lethality administered p.o. up to 20 g/kg in divided doses but the i.p. LD50 was 1122.0 mg/kg. At TD, DAS-77 produced significant (p < 0.05) reductions in body weight, food intake and K+, and increases in ovary weight, neutrophils and HDL, which were reversible. Histopathological presentations were generally normal. Effects at the other doses were comparable to those at TD except for reversible increases in antioxidants in the liver, kidney and testes, and sperm abnormality, and reductions in liver enzymes, sperm motility and count.

Conclusions: Findings in this study revealed that DAS-77 is relatively safe with the potential for enhancing in vivo antioxidant activity. However, possibly reversible side-effects include electrolyte imbalance and sterility in males.

Figure 1

Effect of DAS-77 on body weight of male rats. Values are presented as mean ± SEM (n = 7).^ap < 0.05, ^bp < 0.01, ^cp < 0.001 vs. control (One-way ANOVA followed by Dunnet’s posttest).

Figure 2

Effect of DAS-77 on body weight of female rats. Values are presented as mean ± SEM (n = 3). ^ap < 0.05, ^bp < 0.01, ^cp < 0.001 vs. control (One-way ANOVA followed by Dunnet’s posttest).

Figure 3

Effect of DAS-77 on daily food intake. Values are presented as mean ± SEM (n = 7). ^ap< 0.05, ^bp < 0.01, ^cp < 0.001 vs. control (One-way ANOVA followed by Bonferroni posttests).

Figure 4

Effect of DAS-77 on daily water intake. Values are presented as mean ± SEM (n = 7). ^cp < 0.001 vs. control (One-way ANOVA followed by Bonferroni posttests).

Figure 5

Distilled water group showing the liver (normal) (× 400).

Figure 6

DAS-77 (80 mg/kg) group showing the Liver (normal) (× 400).

Figure 7

DAS-77 (400 mg/kg) group showing the liver (congested) (× 400).

Figure 8

DAS-77 (2000 mg/kg) group showing the liver (congested) (× 400).

Figure 9

Distilled water group showing the brain (normal) (× 400).

Figure 10

DAS-77 (80 mg/kg) group showing the brain (normal) (× 400).

Figure 11

DAS-77 (400 mg/kg) group showing the brain (cerebral oedema).

Figure 12

DAS-77 (2000 mg/kg) group showing the brain (normal) (× 400).

Figure 13

Distilled water group showing the spleen (normal) (× 400).

Figure 14

DAS-77 (80 mg/kg) group showing the spleen (congested) (× 400).

Figure 15

DAS-77 (400 mg/kg) group showing the spleen (congested) (× 400).

Figure 16

DAS-77 (2000 mg/kg) group showing the spleen (congested) (× 400).