Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae) in rodents

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Abstract

Flabellaria paniculata Cav. (Malpighiaceae) is a climbing shrub, the preparations of which are used in the treatment of wounds and ulcers in Nigeria and Ghana. This study investigated the sub-chronic toxicity profile of the hydroethanolic leaf extract of F. paniculata (HLE-FP). HLE-FP was administered p.o. (20, 100, and 500 mg/kg) for 30 and 60 days to different groups of rats. Control animals received 10 ml/kg distilled water. In the group of animals for reversibility study, HLE-FP administration ceased on the 60th day and animals were monitored for a further 15 days. Results showed that oral treatment with HLE-FP for 30 days caused significant (p < 0.05) reductions in weight gain pattern compared to control. These changes were sustained with 60 days treatment. However, no significant (p > 0.05) differences in relative organ weights between control and treatment groups were observed. HLE-FP-treated rats showed significant (p < 0.05) increases in Hb, PCV and RBC on day 30 and significant (p < 0.05) increases in MCV and MCH indices on day 60 compared to control. There were significant (p < 0.05) elevations in serum K+, urea and creatinine compared to control. The liver function tests showed slight but non-significant alterations in relevant parameters when compared to control. Biochemical findings were supported by histopathological observations of vital organs including the kidney and liver. Toxicities observed in respect of kidney function were irreversible at 15 days of stoppage of treatment. In the acute toxicity study, HLE-FP given p.o. caused no lethality at 5000 mg/kg but behavioral manifestations like restlessness, generalized body tremor, feed, and water refusal were observed. The i.p. LD50 was estimated to be 2951.2 mg/kg. Findings in this study showed that HLE-FP is relatively non-toxic on acute exposure and generally safe on sub-chronic administration, but could be deleterious on the kidneys on prolonged oral exposure at a high dose. Thus, caution should be exercised with its long-term usage. © 2014 Akindele, Adeneye, Salau, Sofidiya and Benebo.

Figures

  • Table 1 | Effect of HLE-FP on body weight in the sub-chronic oral toxicity study.
  • Table 4 | Effect of HLE-FP on other serum biochemical parameters in the sub-chronic oral toxicity study.
  • Table 5 | Effect of HLE-FP on hematological parameters in the sub-chronic oral toxicity study.
  • FIGURE 1 | Representative sections of rat lungs in respect of 30 days treatment. (A) Normal rat lung showing normal alveoli and lung parenchyma; (B) 20 mg/kg/day HLE-FP-treated lung showing hyperplasia of the alveolar septae resulting in thickened alveolar space; (C) 100 mg/kg/day HLE-FP-treated lung showing alveolar space smaller than that of control; and (D) 500 mg/kg/day HLE-FP-treated lung showing alveolar space remarkably smaller than that of control (×100 magnification).
  • FIGURE 3 | Representative sections of rat kidneys in respect of 60 days treatment. (A) Normal rat kidney showing regular tubular cells with normal nuclei; (B) 20 mg/kg/day HLE-FP-treated rat kidney showing glomeruli with capillary vascular congestion; (C) 100 mg/kg/day HLE-FP-treated rat kidney showing regular glomeruli with scattered localized hemorrhage; and (D) 500 mg/kg/day HLE-FP-treated rat kidney showing regular glomeruli and tubules with moderate vascular congestion (× 100, × 400 magnification).
  • FIGURE 2 | Representative sections of rat liver in respect of 60 days treatment. (A) Normal rat liver showing normal hepatic architecture; (B) 20 mg/kg/day HLE-FP-treated rat liver showing patchy areas of lymphocytic infiltrations; (C) 100 mg/kg/day HLE-FP-treated rat liver showing mild vascular congestion; and (D) 500 mg/kg/day HLE-FP-treated rat liver showing scattered areas of lymphocytic aggregates with mild sinusoidal congestion signifying mild-to-moderate inflammation (× 100 magnification).
  • FIGURE 4 | Representative sections of rat heart in respect of 60 days treatment. (A) Normal rat heart showing normal cardiac myocytes and fascicules; (B) 20 mg/kg/day HLE-FP-treated rat heart showing few lymphocytic infiltrations around the cardiac myocytes and fascicules; (C) 100 mg/kg/day HLE-FP-treated rat heart showing no remarkable histological lesions; and (D) 500 mg/kg/day HLE-FP-treated rat heart showing occasional lymphocytic aggregates around the cardiac myocytes (× 100 magnification).
  • FIGURE 5 | Representative sections of rat liver in respect of reversibility study. (A) Normal rat liver showing normal hepatocytes and hepatic vasculature; (B) 20 mg/kg/day HLE-FP-treated rat liver showing epithelial proliferation and scattered areas of vascular congestion; (C) 100 mg/kg/day HLE-FP-treated rat liver showing scattered areas of vascular congestion; and (D) 500 mg/kg/day HLE-FP-treated rat liver showing few local lymphocytic aggregates with mild-to-moderate vascular congestion (× 100 magnification).

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APA

Akindele, A. J., Adeneye, A. A., Salau, O. S., Sofidiya, M. O., & Benebo, A. S. (2014). Dose and time-dependent sub-chronic toxicity study of hydroethanolic leaf extract of Flabellaria paniculata Cav. (Malpighiaceae) in rodents. Frontiers in Pharmacology, 5 APR. https://doi.org/10.3389/fphar.2014.00078

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