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Cadmium (Cd), a potent cardiotoxic environmental heavy metal, induces oxidative stress and membrane disturbances in cardiac myocytes. Phosphodiesterase (PDEs) retards the positive inotropic effects of β-adrenoceptor activation by decreasing levels of cAMP via degradation. Hence, PDE inhibitors sensitize the heart to catecholamine and are therefore, used as positive inotropic agents. The present study was designed to probe the potential attenuating effects of the selective PDE4 inhibitor (Roflumilast, ROF), on cardiac biomarkers, lipid profile, lipid peroxidation products, antioxidant status and histology of cardiac tissues against Cd-induced cardiotoxicity in rats. Rats were randomly distributed into four different groups: group 1, served as the normal control group. Group 2, served as the toxic control group and were administered Cd (3 mg/kg, i.p.) for next 7 days. Groups 3 and 4, served as treatment groups that received Cd with concomitant oral administration of ROF doses (0.5 and 1.5 mg/kg), respectively for 7 days. Serum samples of toxic control group rats resulted in significant (P < 0.001) increase in lactate dehydrogenase (LDH), creatine phosphokinase (CPK), total cholesterol (TC), triglycerides (TG) and low density lipoproteins (LDL) levels with concomitant decrease in high density lipoproteins (HDL) levels in serum which were found reversed with both of ROF treatment groups. Cd also causes significant increased (P < 0.001) in myocardial malondialdehyde (MDA) contents while cardiac glutathione (GSH) level, superoxide dismutase (SOD) and catalase (CAT) enzyme activities were found decreased whereas both doses of ROF, significantly reversed these oxidative stress markers and antioxidant enzymes. Cardiotoxicity induced by Cd also resulted in enhanced expression of non-phosphorylated and phosphorylated form of NF-κB p65 and decreased expression of glutathione-S-transferase (GST) and NQO1 which were found reversed with ROF treatments, comparable to normal control group. Histopathological changes were also improved by ROF administration as compared to Cd treated rats alone. In conclusion, Roflumilast exhibited attenuating effect against Cd-induced cardiac toxicity. [ABSTRACT FROM AUTHOR]

The purpose of the research was to examine the protective effect of essential oil from Thymus serrulatus Hochst. ex Benth. (TSA oil) against cadmium (Cd)-induced renal toxicity. The experimental protocol was designed using 30 healthy adult Wistar albino rats allocated into five groups containing six animals in each group. Group 1 was treated as normal control and groups 2, 3, 4, and 5 were treated with cadmium chloride (CdCl2, 3 mg/kg, IP) for 7 days. Group 3 was also treated with silymarin (100 mg/kg, PO) as a standard group, while groups 4 and 5 were administered with TSA oil at doses of 100 and 200 mg/kg PO, respectively. The nephrotoxicity was measured with various parameters such as kidney function markers, oxidative stress markers (glutathione (GSH) and malondialdehyde (MDA)), and messenger ribonucleic acid (mRNA) expression levels of inflammatory factors. The histological studies were also evaluated in the experimental protocol. The CdCl2-treated groups showed a significant increase in the levels of serum kidney function markers along with MDA levels in kidney homogenate. However, renal GSH level was found to be reduced significantly. It was found that CdCl2 significantly upregulated the nuclear factor levels of kappaB (NF-κB p65), inducible nitric oxide synthase (iNOS), and small mothers against decapentaplegic (Smad2) as compared to the normal control group. On the other hand, TSA oil significantly improved the increased levels of serum kidney function markers, non-enzymatic antioxidants, and lipid peroxidation. In addition, TSA oil significantly downregulated the increased expression of NF-κB p65, iNOS, and Smad2 in Cd-intoxicated rats. Moreover, the histological changes in the tissue samples of the kidney of Cd-treated groups were significantly ameliorated in the silymarin- and TSA-oil-treated groups. The present study reveals that TSA oil ameliorates Cd-induced renal injury, and it is also proposed that the observed nephroprotective effect could be due to the antioxidant potential of TSA oil and healing due to its anti-inflammatory action. [ABSTRACT FROM AUTHOR]