Perfluoroundecanoic acid induces DNA damage, reproductive and pathophysiological dysfunctions via oxidative stress in male Swiss mice.

Perfluoroundecanoic acid (PFUnA) is an eleven carbon-chain compound that belongs to the perfluoroalkyl carboxylic acid family. It has been detected in the human blood, effluents, and surface/ground waters, but its toxic effects to the DNA and reproductive system remain unclear. This study was aimed at exploring the toxicity of PFUnA on the hepatic DNA, organ-system and reproductive system in orally treated male Swiss mice. In this present study, administration of PFUnA for 28 days with five doses (0.1, 0.3, 05, 0.7 and 1.0 mg kg-1 b.w./d) in male Swiss mice induced significant hepatic DNA damage which was observed using the alkaline comet assay and equally altered hematological and clinical biochemical parameters. In addition to testicular atrophy, sperm count and sperm motility significantly decreased while sperm abnormalities increased after 35 days exposure. Serum LH and FSH levels were remarkably increased while serum testosterone levels were strikingly reduced. Histopathology revealed the liver, kidney, and testis as potential targets of PFUnA toxicity. Increased activities of superoxide dismutase (SOD) and catalase (CAT), as well as levels of glutathione-s-transferase (GST) and reduced glutathione (GSH), with consistent reduction of glutathione peroxidase (GPx) and reduced glutathione (GSH) in the liver and testis induced oxidative stress. In conclusion, PFUnA exhibited both genotoxicity and reproductive toxicity via oxidative stress induction.

The first-line antituberculosis drugs, and their fixed-dose combination induced abnormal sperm morphology and histological lesions in the testicular cells of male mice.

Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA), and/or their fixed-dose combination (FDC) are extensively prescribed in the cure of Tuberculosis (TB) globally. In spite of the beneficial effect, these drugs are capable of inducing cellular toxicity. Existing information on the genotoxic effects of the first-line anti-TB drugs is limited and contentious. Herein, we evaluated the reproductive genotoxicity of RIF, INH, EMB, PZA, and their FDC utilizing the mouse sperm morphology assay. Histological examination of the testes of exposed mice was also performed. Male Swiss albino mice (11-13 weeks old) were intraperitoneally exposed for 5 consecutive days to each of the anti-TB drugs at four different doses of 6.25, 12.5, 25, and 50 mg/kg bw of PZA; 2.5, 5.0, 10, and 20 mg/kg bw of RIF; 1.25, 2.5, 5.0 and 10 mg/kg bw of INH; 3.75, 7.5, 15 and 30 mg/kg bw of EMB; and 7, 14, 28 and 56 mg/kg bw of FDC corresponding respectively to ×0.25, ×0.5, ×1 and ×2.0 of the standard daily dose. In comparison with the negative control (normal saline), there was no significant difference in the testicular weight and organo-somatic index of exposed mice. There was an increase (p > 0.05) in the frequency of abnormal spermatozoa at most of the tested doses of each drug and a dose-dependent decrease with the FDC. Each of the anti-TB drugs except the FDC induced pathological lesions in the testes. These findings suggest that the individual first-line anti-TB drug unlike the FDC has the potential to provoke testicular anomalies in male mice.

Exposure to a contaminated tropical freshwater (Awba Dam) in Ibadan, Nigeria, induced cytogenotoxicity and haemato-pathological changes in Clarias gariepinus.

Awba reservoir serves the purpose of water supply in the University of Ibadan, Nigeria. Recent reports on pollution status have focused on toxicological implication of contaminants in this reservoir. But none is on genetic and systemic toxicity of the water in fish. We investigated cytogenotoxicity of Awba Dam water (ADW) on Clarias gariepinus using piscine micronucleus (MN) assay. Haematological and histopathological changes were also evaluated. Bi-monthly composite water samples were collected from the reservoir from July to October, 2018. The water was used to cultivate juvenile C. gariepinus in the laboratory for 1-4 months, and tap water was used as the negative control. Peripheral blood erythrocytes from the caudal veins of C. gariepinus were used for the monthly MN assessment. There was significant (p < 0.05) induction of MN and other erythrocyte nuclear abnormalities in C. gariepinus within the period of study. There were variations in the haematological indices and pathological alterations in sections of the gill, liver and kidney of C. gariepinus. The levels of some heavy metals in ADW were above standard permissible limits and might have contributed to the observed cytogenetic and systemic disruptions. These findings may be used by the concerned authorities to evolve management strategies for the reservoir's health and biologic resources.

Titanium dioxide nanoparticles-induced cytogenotoxicity and alterations in haematological indices of Clarias gariepinus (Burchell, 1822).

The application of titanium dioxide (TiO2) nanoparticles (NPs) in the manufacturing of consumer products has increased tremendously and with the potential to induce deleterious effects on aquatic biota. There have been reports on metal oxide NP toxicity in aquatic organisms, however, information on cytotoxicity and genotoxicity of TiO2 NPs on the African catfish, Clarias gariepinus, is scarce. In this study, we investigated the genotoxicity and haematotoxicity of TiO2 NPs in C. gariepinus using the micronucleus (MN) assay and haematological analysis, respectively. Juvenile C. gariepinus were exposed to 6.25, 12.5, 25.0, 50.0 and 100.0 mg L-1 concentrations of TiO2 NPs for 7 and 28 days. Benzene (0.05 mL L-1) and dechlorinated tap water were used as positive and negative controls, respectively. Data of the MN showed a significant (p < 0.05) concentration-dependent increase in the frequency of MN at both exposure periods in comparison to negative control. Red blood cells, haematocrit, platelets and heterophils significantly reduced with an increased mean corpuscular haemoglobin concentration and lymphocytes at the 7-day exposure period, while in the 28-day exposure period, mean cell volume, mean corpuscular haemoglobin and lymphocytes had a significant increase in comparison with the negative control. This study indicates that TiO2 NPs induced cytogenetic and haematological alterations in C. gariepinus and is of relevance in biodiversity and aquatic health management.

Alteration of sperm parameters and reproductive hormones in Swiss mice via oxidative stress after co-exposure to titanium dioxide and zinc oxide nanoparticles.

In this study, Swiss male mice were intraperitoneally administered with titanium dioxide (TiO2 ) and zinc oxide (ZnO) nanoparticles (NPs) and their mixture (1:1) at doses between 9.38 and 75 mg/kg for 5 weeks to evaluate reproductive toxicity. Both NPs and their mixture significantly (p < .001) altered sperm motility, reduced sperm numbers and increased abnormalities, while their mixture induced more sperm abnormalities than either TiO2 NPs or ZnO NPs. Both NPs and their mixture significantly (p < .05) reduced the LH level, while ZnO NPs alone and their mixture (p < .001) increased the testosterone levels at tested doses. The testes of exposed mice showed pathological changes and altered histomorphometrics. TiO2 NPs and ZnO NPs individually induced a significant (p < .01) reduction in SOD and CAT activities, while the mixture significantly (p < .001) decreased CAT activity and increased SOD activity. TiO2 NPs alone at 9.38 mg/kg induced a significant (p < .001) reduction in the GSH level, while both NPs and their mixture increased the MDA level significantly (p < .05). The data showed that the mixture had a synergistic interaction to induce testicular damage. Overall, oxidative stress may be involved in the NP-mediated testicular damage observed.

Genetic and systemic toxicity induced by silver and copper oxide nanoparticles, and their mixture in Clarias gariepinus (Burchell, 1822).

Unanticipated increase in the use of silver (Ag) and copper oxide (CuO) nanoparticles (NPs) due to their antimicrobial properties is eliciting environmental health concern because of their coexistence in the aquatic environment. Therefore, we investigated the genetic and systemic toxicity of the individual NPs and their mixture (1:1) using the piscine micronucleus (MN) assay, haematological, histopathological (skin, gills and liver) and hepatic oxidative stress analyses [malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT)] in the African mud catfish, Clarias gariepinus. The fish were exposed to sublethal concentrations (6.25-100.00 mg/L) of each NP and their mixture for 28 days. Both NPs and their mixture induced significant (p < 0.05) increase in MN frequency and other nuclear abnormalities. There was significant decrease in haemoglobin concentration, red and white blood cell counts. Histopathological lesions observed include epidermal skin cells and gill lamellae hyperplasia and necrosis of hepatocytes. The levels of MDA, GSH and activities of SOD and CAT were impacted in C. gariepinus liver following the exposure to the NPs and their mixture. Interaction factor analysis of data indicates antagonistic genotoxicity and oxidative damage of the NPs mixture. These results suggest cytogenotoxic effects of Ag NPs, CuO NPs and their mixture via oxidative stress in Clarias gariepinus.