H1 antihistamines are the most widely used drugs for relieving symptoms of histamine-mediated disease. Although chlorpheniramine maleate and cetirizine hydrochloride have tolerable side effects, they induce severe side effects on chronic use such as hepatitis and cholestatic jaundice. Oxidative stress has been implicated as a mechanism of drug-induced hepatotoxicity. LCarnitine is an effective biological active compound that is involved in oxidation of fatty acids in the liver through transportation of fatty acids into the mitochondria for energy production from fat. L-Carnitine has well-known antioxidant properties, improves hepatic function, and improves mitochondrial function in hepatic cells. In the present study, we evaluated the possible role of oxidative stress and the therapeutic and hepatoprotective effect of L-carnitine on chlorpheniramine maleate– and cetirizine hydrochloride–induced liver damage during chronic use. Methods are measurement of ALT, AST, ALP and albumin serum levels and measurement of hepatic oxidative stress biomarkers MDA and GSH in groups with and without combination with Lcarnitine. Histopathological examination of changes in hepatic tissue and scoring of the induced hepatic damage was conducted in all treatment groups. Co-treatment of L-carnitine with chlorpheniramine maleate and cetirizine hydrochloride significantly improved the deteriorated hepatic function as indicated by reduction in the serum levels of ALT, AST, ALP, and elevation in serum albumin levels compared with control and untreated groups. Moreover, co-administration of L-carnitine with chlorpheniramine maleate and cetirizine hydrochloride decreased hepatic MDA and elevated hepatic GSH levels compared with control and untreated groups. Ultrastructure examination of hepatic tissue found that co-treatment with L-carnitine decreased hepatic necrosis and damage. In conclusion, oxidative stress can be a possible explanation of hepatic damage induced by chronic therapy with chlorpheniramine maleate and cetirizine hydrochloride. L-Carnitine has prominent hepatoprotective effects on chlorpheniramine maleate– and cetirizine hydrochloride–induced hepatic damage possibly through improvement of hepatic function and decreasing oxidative stress.

The current study was undertaken to explain the cytogenetic and genotoxic effects of penconazole (PEN) fungicide and chlorpyrifos (CPF) insecticide in male rats. Rats (n=10/group) were treated with 500 mg/kg body weight PEN orally for 24 h, 48 h and 100 mg/kg body weight for 30 days and the control animals were administered distilled water only. Chlorpyrifos exposed groups received 39 mg/kg body weight for 24 h and 48 h and 8 mg/kg body weight for 30 days by oral gavage and the control group was received corn oil. Blood samples were collected for complete blood count. Bone marrow was flushed from the femur bones for chromosomal aberration (CA) and comet assay. Spleen samples were preserved in 10% formalin for histopathological examination. The level of DNA damage was measured using DNA damage index. The results showed that PEN and CPF caused significant hematological changes, significant increase in DNA damage index and increased the number of nuclei with I, II, III and IV degrees of damage. Different types of CA were recorded in PEN and CPF exposed groups including chromosomal break, deletion, attenuation, chromosome ring, gap and fragments. In addition, numerical aberration as polyploidy appeared in CPF exposed groups only. PEN and CPF caused histopathological changes in spleen in the form of apoptosis, congestion, thrombosis and hemosiderosis. In conclusion, PEN and CPF induced genotoxic and cytogenetic effects in bone marrow. DNA damage index and the percentage of CA were higher in CPF than PEN groups.

The current study was undertaken to explain the cytogenetic and genotoxic effects of penconazole (PEN) fungicide and chlorpyrifos (CPF) insecticide in male rats. Rats (n=10/group) were treated with 500 mg/kg body weight PEN orally for 24 h, 48 h and 100 mg/kg body weight for 30 days and the control animals were administered distilled water only. Chlorpyrifos exposed groups received 39 mg/kg body weight for 24 h and 48 h and 8 mg/kg body weight for 30 days by oral gavage and the control group was received corn oil. Blood samples were collected for complete blood count. Bone marrow was flushed from the femur bones for chromosomal aberration (CA) and comet assay. Spleen samples were preserved in 10% formalin for histopathological examination. The level of DNA damage was measured using DNA damage index. The results showed that PEN and CPF caused significant hematological changes, significant increase in DNA damage index and increased the number of nuclei with I, II, III and IV degrees of damage. Different types of CA were recorded in PEN and CPF exposed groups including chromosomal break, deletion, attenuation, chromosome ring, gap and fragments. In addition, numerical aberration as polyploidy appeared in CPF exposed groups only. PEN and CPF caused histopathological changes in spleen in the form of apoptosis, congestion, thrombosis and hemosiderosis. In conclusion, PEN and CPF induced genotoxic and cytogenetic effects in bone marrow. DNA damage index and the percentage of CA were higher in CPF than PEN groups.

Montelukast (MNK) has prominent anti-inflammatory and antioxidant activities. It can protect the liver in different hepatotoxic models in animals. Simvastatin (SMV) is one of commonly used lipid lowering drugs for treatment of dyslipidemia in order to reduce cardiovascular disease. It has severe side effects such as myopathy and hepatotoxicity. The aim of the present study is to investigate the possible effect of MNK on SMV-induced myopathy and hepatotoxicity. Four groups of male rats: control group which received saline via stomach tube, MNK treated group (received 10 mg/kg/day MNK via stomach tube), SMV treated group (received 30 mg/kg/day SMV via stomach tube), and MNK + SMV (combination) group which received both MNK and SMV. All animals were treated for 14 days before obtaining blood and tissue samples. SMV has both hepatotoxic effects and myopathy. SMV caused a significant increase in myoglobin, creatinine kinase, ALT, AST, ALP, and bilirubin but, it decreased total proteins, globulin and albumin levels. Co-treatment of SMV and MNK increased the antioxidant activity significantly. MNK modifies partially the myopathic changes and hepatotoxic effect of SMV. Co-administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney. They have antioxidant activities when given together that producemuscle and hepatic protective effects.

Montelukast (MNK) has prominent anti-inflammatory and antioxidant activities. It can protect the liver in different hepatotoxic models in animals. Simvastatin (SMV) is one of commonly used lipid lowering drugs for treatment of dyslipidemia in order to reduce cardiovascular disease. It has severe side effects such as myopathy and hepatotoxicity. The aim of the present study is to investigate the possible effect of MNK on SMV-induced myopathy and hepatotoxicity. Four groups of male rats: control group which received saline via stomach tube, MNK treated group (received 10 mg/kg/day MNK via stomach tube), SMV treated group (received 30 mg/kg/day SMV via stomach tube), and MNK + SMV (combination) group which received both MNK and SMV. All animals were treated for 14 days before obtaining blood and tissue samples. SMV has both hepatotoxic effects and myopathy. SMV caused a significant increase in myoglobin, creatinine kinase, ALT, AST, ALP, and bilirubin but, it decreased total proteins, globulin and albumin levels. Co-treatment of SMV and MNK increased the antioxidant activity significantly. MNK modifies partially the myopathic changes and hepatotoxic effect of SMV. Co-administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney. They have antioxidant activities when given together that producemuscle and hepatic protective effects.

Montelukast (MNK) has prominent anti-inflammatory and antioxidant activities. It can protect the liver in different hepatotoxic models in animals. Simvastatin (SMV) is one of commonly used lipid lowering drugs for treatment of dyslipidemia in order to reduce cardiovascular disease. It has severe side effects such as myopathy and hepatotoxicity. The aim of the present study is to investigate the possible effect of MNK on SMV-induced myopathy and hepatotoxicity. Four groups of male rats: control group which received saline via stomach tube, MNK treated group (received 10 mg/kg/day MNK via stomach tube), SMV treated group (received 30 mg/kg/day SMV via stomach tube), and MNK + SMV (combination) group which received both MNK and SMV. All animals were treated for 14 days before obtaining blood and tissue samples. SMV has both hepatotoxic effects and myopathy. SMV caused a significant increase in myoglobin, creatinine kinase, ALT, AST, ALP, and bilirubin but, it decreased total proteins, globulin and albumin levels. Co-treatment of SMV and MNK increased the antioxidant activity significantly. MNK modifies partially the myopathic changes and hepatotoxic effect of SMV. Co-administration of MNK and SMV decreased their toxic potentials on the liver, skeletal muscles, and kidney. They have antioxidant activities when given together that producemuscle and hepatic protective effects.

Methotrexate (MTX) is mainly used as antimetabolite agents in cancer therapy. It causes serious side effects such as nephrotoxicity, hepatotoxicity, and anemia. Nigella sativa (NS) is a medicinal herb that has protective effects against the MTX-related side effects. The study aimed to determine the optimal concentration of the combination of NS-MTX mixture to improve the antitumor effects of MTX and reduce its related adverse effects. In this study, in vitro evaluation of anti-tumor and anti-angiogenic activities ofNS,MTX, or their mixture in different concentrations using liver hepatocellular carcinoma and endothelial cells were performed. The protective effects of NS on normal hepatic and kidney cells against the risks of MTX treatment was also tested in vitro. Moreover, for in vivo evaluation, male Wistar rats were treated with MTX or a combination of MTX and NS. Hematological and serological, biochemical, functional, and histopathological studies were performed. The results showed that the low concentration of NS enhanced the anti-tumor and anti-angiogenic effects ofMTX.Moreover, it had protective effects on normal hepatic and kidney cells against toxicity induced by MTX treatments. The in vivo results showed significant improvements in the blood condition and liver functional parameters in MTX-intoxicated rats after treating with NS. NS reduced the oxidative stress indices in both kidney and liver tissues. The histopathological examinations showed that NS reduced degenerative changes and necrosis in both kidney and liver. These results suggested that NS in low concentration could improve the efficacy and the safety of MTX treatment.

Methotrexate (MTX) is mainly used as antimetabolite agents in cancer therapy. It causes serious side effects such as nephrotoxicity, hepatotoxicity, and anemia. Nigella sativa (NS) is a medicinal herb that has protective effects against the MTX-related side effects. The study aimed to determine the optimal concentration of the combination of NS-MTX mixture to improve the antitumor effects of MTX and reduce its related adverse effects. In this study, in vitro evaluation of anti-tumor and anti-angiogenic activities ofNS,MTX, or their mixture in different concentrations using liver hepatocellular carcinoma and endothelial cells were performed. The protective effects of NS on normal hepatic and kidney cells against the risks of MTX treatment was also tested in vitro. Moreover, for in vivo evaluation, male Wistar rats were treated with MTX or a combination of MTX and NS. Hematological and serological, biochemical, functional, and histopathological studies were performed. The results showed that the low concentration of NS enhanced the anti-tumor and anti-angiogenic effects ofMTX.Moreover, it had protective effects on normal hepatic and kidney cells against toxicity induced by MTX treatments. The in vivo results showed significant improvements in the blood condition and liver functional parameters in MTX-intoxicated rats after treating with NS. NS reduced the oxidative stress indices in both kidney and liver tissues. The histopathological examinations showed that NS reduced degenerative changes and necrosis in both kidney and liver. These results suggested that NS in low concentration could improve the efficacy and the safety of MTX treatment.

Methotrexate (MTX) is mainly used as antimetabolite agents in cancer therapy. It causes serious side effects such as nephrotoxicity, hepatotoxicity, and anemia. Nigella sativa (NS) is a medicinal herb that has protective effects against the MTX-related side effects. The study aimed to determine the optimal concentration of the combination of NS-MTX mixture to improve the antitumor effects of MTX and reduce its related adverse effects. In this study, in vitro evaluation of anti-tumor and anti-angiogenic activities ofNS,MTX, or their mixture in different concentrations using liver hepatocellular carcinoma and endothelial cells were performed. The protective effects of NS on normal hepatic and kidney cells against the risks of MTX treatment was also tested in vitro. Moreover, for in vivo evaluation, male Wistar rats were treated with MTX or a combination of MTX and NS. Hematological and serological, biochemical, functional, and histopathological studies were performed. The results showed that the low concentration of NS enhanced the anti-tumor and anti-angiogenic effects ofMTX.Moreover, it had protective effects on normal hepatic and kidney cells against toxicity induced by MTX treatments. The in vivo results showed significant improvements in the blood condition and liver functional parameters in MTX-intoxicated rats after treating with NS. NS reduced the oxidative stress indices in both kidney and liver tissues. The histopathological examinations showed that NS reduced degenerative changes and necrosis in both kidney and liver. These results suggested that NS in low concentration could improve the efficacy and the safety of MTX treatment.

Methotrexate (MTX) is mainly used as antimetabolite agents in cancer therapy. It causes serious side effects such as nephrotoxicity, hepatotoxicity, and anemia. Nigella sativa (NS) is a medicinal herb that has protective effects against the MTX-related side effects. The study aimed to determine the optimal concentration of the combination of NS-MTX mixture to improve the antitumor effects of MTX and reduce its related adverse effects. In this study, in vitro evaluation of anti-tumor and anti-angiogenic activities ofNS,MTX, or their mixture in different concentrations using liver hepatocellular carcinoma and endothelial cells were performed. The protective effects of NS on normal hepatic and kidney cells against the risks of MTX treatment was also tested in vitro. Moreover, for in vivo evaluation, male Wistar rats were treated with MTX or a combination of MTX and NS. Hematological and serological, biochemical, functional, and histopathological studies were performed. The results showed that the low concentration of NS enhanced the anti-tumor and anti-angiogenic effects ofMTX.Moreover, it had protective effects on normal hepatic and kidney cells against toxicity induced by MTX treatments. The in vivo results showed significant improvements in the blood condition and liver functional parameters in MTX-intoxicated rats after treating with NS. NS reduced the oxidative stress indices in both kidney and liver tissues. The histopathological examinations showed that NS reduced degenerative changes and necrosis in both kidney and liver. These results suggested that NS in low concentration could improve the efficacy and the safety of MTX treatment.