The genotoxicity and systemic toxicity of a pharmaceutical effluent in Wistar rats may involve oxidative stress induction

Abstract

There is scarcity of information on the possible mechanisms of pharmaceutical effluent induced genotoxicity and systemic toxicity. This study investigated the genotoxicity and systemic toxicity of a pharmaceutical effluent in Wistar rats. Rats were orally treated with 5-50% concentrations of the effluent for 28 days. At post-exposure, blood, liver, kidney and bone marrow cells were examined for alterations in serum biochemical parameters and hematological indices, histopathological lesions and micronucleated polychromatic erythrocytes formation (MNPCE). The effluent caused concentration independent significant (p < 0.05) alterations in aspartate (AST) and alanine (ALT) aminotransferases, superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total and direct bilirubin and creatinine. There was reduction in red blood count (RBC), hemoglobin concentration (HGB), platelets, percentage hematocrit (HCT), white blood count (WBC) and mean corpuscle hemoglobin (MCH) except mean corpuscle hemoglobin concentration (MCHC), which increased in the treated rats. Histopathological lesions observed in the liver and kidney of the effluent treated rats were thinning of the hepatic cord, kuffer cell hyperplasia, vacuolation of the hepatocytes and renal cells, multifocal inflammatory changes, necrosis and congestion of the renal blood vessels and central vein. MNPCE significantly increase in the bone marrow of the treated rats compared to the negative control. The concentration of some toxic metals and anions in the effluent were above standard permissible limits. These findings showed that the pharmaceutical effluent caused somatic DNA damage and systemic toxicity in rats may involve induction of oxidative stress, suggesting environmental contamination and health risks in wildlife and humans.

Keywords: Biochemistry; Hematology; Histopathology; Micronucleus test; Pharmaceutical effluents; Rats.

Fig. 1

Effects of pharmaceutical effluent on serum ALT and AST activities. End point represents mean ± SD for 5 rats. Values are significantly different *p < 0.05 compared to the corresponding negative controls. DW – Distilled Water; CYP – Cyclophosphamide (40 mg/Kg bwt).

Fig. 2

Effects of pharmaceutical effluent on micronuclei polychromatic erythrocyte formation (MNPCE). End point represents mean ± SD for 5 rats. Values are significantly different *p < 0.05 compared to the corresponding negative controls. DW – Distilled Water; CYP – Cyclophosphamide (40 mg/Kg bwt).

Fig. 3

Sections of the liver from rat exposed to pharmaceutical effluent (H&E, ×400). (a) liver from rat in the negative control group showing apparently normal hepatocytes. (b) thinning of the hepatocytic cord with moderate kuffer cell hyperplasia (arrow). (c) Vacuolations of the hepatocytes (arrow) and necrosis (N). (d) Multifocal inflammatory cellular (MI) and vacuolar changes in the hepatoctes along with congestion of the central vein (C).

Fig. 4

Sections of the kidney from rats exposed to pharmaceutical effluent (H&E, ×400). (a) kidney from a negative control rat showing apparently normal cortical and medullary section of the nephron. (b) Marked congestion of the renal blood vessels (arrow). (c) Swollen epithelium with congestions of the renal interstitium (arrow). (d) Vacuolar changes of the tubular epithelium cells (arrow) and fibroplastic proliferation (FP).