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Background/Aims: Lipopolysaccharide (LPS) induces acute lung injury (ALI) through oxidative stress and inflammation. Naringenin exerts antioxidant and anti-inflammatory effects. The possible protective effect of naringenin was investigated against ALI induced by LPS in rats. Methods: Rats received a single injection of LPS (5 mg/kg, i.v.). Naringenin was given for 4 consecutive days, at 2 doses (50 and 100 mg/kg/day, p.o.), starting 3 days before LPS administration. Results: LPS significantly increased wet/dry lung weight ratio, malondialdehyde, nitric oxide (NO), interleukin-6, and myeloperoxidase activity in the lung tissues. Naringenin, particularly the higher dose, significantly ameliorated the LPS-induced changes in the measured parameters. Also, naringenin markedly reduced the histopathological lung tissue injury that resulted from LPS. Naringenin significantly decreased the LPS-induced expression of nuclear factor-κB, inducible NO synthase, tumor necrosis factor-a, caspase-3, and significantly increased heat shock protein 70 expression in the lungs. Conclusion: Naringenin significantly protected against LPS-induced ALI in rats through its anti-inflammatory, antioxidant, antinitrosative, and antiapoptotic effects.

Oxidative/nitrosative stress, inflammation, and apoptosis play a crucial role in the pathogenesis of arsenic-induced testicular injury. Telmisartan, the angiotensin II-receptor antagonist, possesses antioxidant and anti-inflammatory activities. The protective effect of telmisartan against arsenic-induced testicular damage was investigated in rats. Testicular damage was induced by sodium arsenite (10 mg kg–1/day, p.o., for 2 consecutive days). Telmisartan (10 mg kg–1/day, i.p.) was given for 3 consecutive days, starting 1 day before sodium arsenite administration. Telmisartan significantly attenuated the arsenic-induced decrease in the levels of serum testosterone and testicular reduced glutathione, and significantly decreased the elevation of the levels of testicular malondialdehyde, nitric oxide, and arsenic levels, as well as myeloperoxidase activity resulting from sodium arsenite administration. Histopathological and immunohistochemical examination revealed that telmisartan markedly attenuated testicular tissue changes, and decreased the arsenic-induced expression of vascular endothelial growth factor, inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, and caspase-3. Telmisartan, via its antioxidant and/or anti-inflammatory effects, may represent a potential candidate to protect against the deleterious effects of arsenic on testicular tissue.

The potential protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against doxorubicin cardiotoxicity in rats. Cardiotoxicity was induced by six equal doses of doxorubicin (2.5mgkg(-1) i.p., each) given at 48h intervals over two weeks to achieve a total dose of 15mgkg(-1). Cannabidiol treatment (5mgkg(-1)/day, i.p.) was started on the same day of doxorubicin administration and continued for four weeks. Cannabidiol significantly reduced the elevations of serum creatine kinase-MB and troponin T, and cardiac malondialdehyde, tumor necrosis factor-α, nitric oxide and calcium ion levels, and attenuated the decreases in cardiac reduced glutathione, selenium and zinc ions. Histopathological examination showed that cannabidiol ameliorated doxorubicin-induced cardiac injury. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in cardiac tissue of doxorubicin-treated rats. These results indicate that cannabidiol represents a potential protective agent against doxorubicin cardiac injury.

The therapeutic potential of coenzyme Q10 was investigated in rats with hepatocellular carcinoma induced by trichloroacetic acid (0.5g/kg/day, p.o., for five days). Coenzyme Q10 treatment (0.4mg/kg/day, i.p.) was applied for four weeks following trichloroacetic acid administration. Coenzyme Q10 significantly suppressed lipid peroxidation, prevented the depletion of reduced glutathione and superoxide dismutase activity, and decreased the elevations of tumor necrosis factor-α and nitric oxide in liver tissue of rats with hepatocellular carcinoma. Also, the histopathological dysplastic changes induced by trichloroacetic acid in liver tissue were ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the expression of hepPar-1, alpha-fetoprotein, inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor-κB in liver tissue of rats with hepatocellular carcinoma. It was concluded that coenzyme Q10 may represent a potential therapeutic option for liver carcinogenesis.

The present study investigated the protective effect of thymoquinone (TQ), against cadmium-induced kidney injury in rats. Cadmium chloride (1.2 mg Cd/kg/day, s.c.), was given for nine weeks. TQ treatment (40 mg/kg/day, p.o.) started on the same day of cadmium administration and continued for nine weeks. TQ significantly decreased serum creatinine, renal malondialdehyde and nitric oxide, and significantly increased renal reduced glutathione in rats received cadmium. Histopathological examination showed that TQ markedly minimized renal tissue damage induced by cadmium. Immunohistochemical analysis revealed that TQ markedly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, and caspase-3 in renal tissue. It was concluded that TQ significantly protected against cadmium nephrotoxicity in rats, through its antioxidant, antiinflammatory, and antiapoptotic actions.

The therapeutic potential of telmisartan was investigated in mice exposed to acute hepatotoxicity induced by a single dose of acetaminophen (500 mg/kg, p.o.). Telmisartan treatment (two i.p. injections, 10mg/kg, each) was given at 1 and 12h following acetaminophen administration. Telmisartan significantly reduced the level of serum alanine aminotransferase, and suppressed lipid peroxidation, prevented the depletion of the antioxidant defenses (reduced glutathione level, and catalase and superoxide dismutase activities), and attenuated the elevation of nitric oxide resulted from acetaminophen administration. Also, telmisartan ameliorated the histopathological liver tissue damage induced by acetaminophen. Immunohistochemical analysis revealed that telmisartan significantly decreased the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue of mice received acetaminophen overdose. In conclusion, telmisartan can be considered as a potential therapeutic option to protect against acute acetaminophen hepatotoxicity commonly encountered in clinical practice.

Objectives To investigate the potential protective effects of captopril, the angiotensin-converting enzyme inhibitor, in diabetic rats exposed to ischaemia/reperfusion (I/R) renal injury. Methods Following successful induction of diabetes, captopril treatment (50 mg/kg/day, p.o.) was applied for 4 weeks, after which bilateral renal ischaemia was induced for 30 min followed by reperfusion for 24 h. Results Captopril significantly attenuated hyperglycaemia and hypoinsulinaemia in diabetic rats, and significantly reduced the elevations of serum creatinine and aldosterone levels, and renal malondialdehyde, tumour necrosis factor-α and nitric oxide (NO), and prevented the depletion of reduced glutathione caused by I/R in diabetic rats. Histopathological renal tissue damage induced by I/R in diabetic rats was ameliorated by captopril treatment. Immunohistochemical analysis revealed that captopril significantly attenuated the reduction of insulin content in pancreatic islet β-cells, and decreased the I/R-induced expression of inducible NO synthase, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin and heme oxygenase-1 in the kidney tissue of diabetic rats. Conclusions Captopril represents a potential candidate to reduce the risk of renal injury induced by ischaemia/reperfusion in type 2 diabetes.

The therapeutic potential of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated in rats exposed to ischemia/reperfusion liver injury. Ischemia was induced by clamping the pedicle of the left hepatic lobe for 30 min, and cannabidiol (5 mg/kg, i.v.) was given 1 h following the procedure and every 24 h thereafter for 2 days. Ischemia/reperfusion caused significant elevations of serum alanine aminotransferase and hepatic malondialdehyde, tumor necrosis factor-α and nitric oxide levels, associated with significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters mediated by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced liver damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin protein in ischemic/reperfused liver tissue. These results emphasize that cannabidiol represents a potential therapeutic option to protect the liver against hypoxia–reoxygenation injury.

The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Summary The protective effect of thymoquinone was investigated against cadmium-induced testicular toxicity in rats. Testicular toxicity was induced by a single intraperitoneal (i.p.) injection of cadmium chloride (2 mg kg−1). Thymoquinone treatment (10 mg kg−1 day−1, i.p.) was applied for five consecutive days, starting 3 days before cadmium administration. Thymoquinone significantly attenuated the cadmium-induced decreases in serum testosterone, and testicular reduced glutathione and superoxide dismutase activity and significantly decreased the elevations of testicular malondialdehyde, nitric oxide and cadmium ion levels resulted from cadmium chloride administration. Also, thymoquinone ameliorated the cadmium-induced testicular tissue injury observed by histopathological examination. In addition, thymoquinone significantly decreased the cadmium-induced expression of inducible nitric oxide synthase, tumour necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in testicular tissue. It was concluded that thymoquinone, through its antioxidant and anti-inflammatory activities, may represent a potential candidate to protect the testes against the detrimental effect of cadmium exposure.

The possible therapeutic effect of cannabidiol, the major non-psychotropic Cannabis constituent, was investigated against acute hepatotoxicity induced by a single oral dose of acetaminophen (500mg/kg) in mice. Cannabidiol (two intraperitoneal injections, 5mg/kg, each) was given 1 hour and 12 hours following acetaminophen administration. Acetaminophen administration caused significant elevations of serum alanine aminotransferase, and hepatic malondialdehyde, and nitric oxide levels, and a significant decrease in hepatic reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters resulted from acetaminophen administration. Also, histopathological examination showed that cannabidiol markedly attenuated ameliorated acetaminophen-induced liver tissue damage. 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Summary Testicular torsion/detorsion induces oxidative/nitrosative stress, inflammation and apoptosis of testicular tissues. Baicalin exerts antioxidant and anti-inflammatory properties. This study investigated the possible protective effect of baicalin against testicular torsion–detorsion injury in rats. Surgical testicular torsion was induced for 2 h, followed by detorsion which was continued for 24 h. Baicalin was administered in three different doses (25, 50 and 100 mg kg−1, by intraperitoneal injection). Each dose was given twice, the first 30 min before and the second 12 h after testicular detorsion. Baicalin, in a dose-dependent manner, decreased the torsion/detorsion-induced elevations of testicular malondialdehyde, nitric oxide, tumour necrosis factor-α, BCL2-associated X protein (Bax), cytosolic cytochrome c and caspase-3 and caspase-9 activities. Baicalin, dose dependently, attenuated the reductions of B-cell leucemia/lymphoma 2 (Bcl-2), and glutathione peroxidase and superoxide dismutase activities in testicular tissues resulted from torsion/detorsion. In addition, baicalin ameliorated the histopathological testicular tissue damage and reduced the expression of Fas ligand in rat testes exposed to torsion/detorsion in a dose-dependent manner. It was concluded that baicalin, dose dependently, ameliorated testicular injury induced by torsion/detorsion via its antioxidant, antinitrosative, anti-inflammatory and anti-apoptotic effects.

The protective effect of telmisartan, the angiotensin II-receptor antagonist, against liver toxicity induced by sodium arsenite (5 mg/kg/day, p.o., for 30 days) was investigated in mice. Telmisartan treatment (10 mg/kg/day, p.o.) was applied for 30 days, starting on the same day of arsenic administration. Telmisartan significantly reduced serum alanine aminotransferase level which was increased by sodium arsenite. Telmisartan significantly suppressed lipid peroxidation, and prevented the reduced glutathione depletion and nitric oxide elevation in the liver tissue resulted from arsenic administration. Also, the increase of arsenic ion, and the reductions of selenium and zinc ions in liver tissue were attenuated by telmisartan. Histopathological examination showed that liver tissue injury mediated by arsenic was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan significantly decreased the arsenic-induced expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB and caspase-3 in liver tissue. It was concluded that telmisartan may represent a potential option to protect the liver tissue from the detrimental effects of arsenic toxicity.

Aims To investigate the protective effect of cannabidiol, the major non-psychotropic Cannabis constituent, against renal ischemia/reperfusion injury in rats. Main methods Bilateral renal ischemia was induced for 30 min followed by reperfusion for 24 h. Cannabidiol (5 mg/kg, i.v.) was given 1 h before and 12 h following the procedure. Key findings Ischemia/reperfusion caused significant elevations of serum creatinine and renal malondialdehyde and nitric oxide levels, associated with a significant decrease in renal reduced glutathione. Cannabidiol significantly attenuated the deterioration in the measured biochemical parameters induced by ischemia/reperfusion. Histopathological examination showed that cannabidiol ameliorated ischemia/reperfusion-induced kidney damage. Immunohistochemical analysis revealed that cannabidiol significantly reduced the expression of inducible nitric oxide synthase, tumor necrosis factor-α, cyclooxygenase-2, nuclear factor-κB, Fas ligand and caspase-3, and increased the expression of survivin in ischemic/reperfused kidney tissue. Significance Cannabidiol, via its antioxidant and anti-inflammatory properties, may represent a potential therapeutic option to protect against ischemia/reperfusion renal injury.

The potential protective effect of coenzyme Q10 against acute liver injury induced by a single dose of acetaminophen (700 mg/kg, p.o.) was investigated in rats. Coenzyme Q10 treatment was given as two i.p. injections, 10 mg/kg each, at 1 and 12 h following acetaminophen administration. Coenzyme Q10 significantly reduced the levels of serum aminotransferases, suppressed lipid peroxidation, prevented the decreases of reduced glutathione and catalase activity, decreased the elevations of tumor necrosis factor-α and nitric oxide as well as attenuating the reductions of selenium and zinc ions in liver tissue resulting from acetaminophen administration. Histopathological liver tissue damage mediated by acetaminophen was ameliorated by coenzyme Q10. Immunohistochemical analysis revealed that coenzyme Q10 significantly decreased the acetaminophen-induced overexpression of inducible nitric oxide synthase, nuclear factor-κB, caspase-3 and p53 in liver tissue. It was concluded that coenzyme Q10 protects rat liver against acute acetaminophen hepatotoxicity, most probably through its antioxidant, anti-inflammatory and antiapoptotic effects.

The possible protective effect of captopril, an angiotensin-converting enzyme inhibitor, vs. telmisartan, an angiotensin II-receptor antagonist, was investigated in rats with testicular injury induced by a single i.p. injection of cadmium chloride (2 mg/kg). Captopril (60 mg/kg/day, p.o.) and telmisartan (10 mg/kg/day, p.o.) were given for five consecutive days, starting 3 days before cadmium administration. Both agents significantly increased serum testosterone level, which was reduced by cadmium, suppressed lipid peroxidation, restored the depleted reduced glutathione, decreased the elevations of nitric oxide, tumor necrosis factor-α, and cadmium ion levels, and attenuated the reductions of selenium and zinc ions in testicular tissue resulted from cadmium administration. Immunohistochemical analysis revealed that both captopril and telmisartan significantly reduced the cadmium-induced expression of inducible nitric oxide synthase, nuclear factor-κB, Fas ligand, and caspase-3 in testicular tissue. The differences between the results obtained with captopril and telmisartan were insignificant, suggesting that both drugs equally protected the testicular tissue from the detrimental effects of cadmium.

Aims To investigate the nephroprotective effect of telmisartan, the angiotensin II receptor antagonist, against renal injury induced by cadmium in mice. Main methods Mice received cadmium chloride at a dose of 1.2 mg Cd/kg/day, s.c., for nine weeks. Telmisartan treatment (1 mg/kg/day, orally) was started one week before cadmium administration and continued for ten weeks. Key findings Telmisartan significantly reduced blood urea nitrogen (BUN) and serum creatinine levels which were increased by cadmium. Also, telmisartan significantly suppressed lipid peroxidation, compensated deficits in the antioxidant defenses [reduced glutathione (GSH) level and catalase activity], decreased the elevations of tumor necrosis factor-α (TNF-α), nitric oxide (NO) and cadmium ion concentration, and attenuated the reductions of selenium and zinc ions in renal tissue resulted from cadmium administration. Histopathological examination revealed that cadmium-induced renal tissue damage was ameliorated by telmisartan treatment. Immunohistochemical analysis revealed that telmisartan significantly decreased the cadmium-induced overexpression of inducible nitric oxide synthase (iNOS), nuclear factor-κB (NF-κB), Fas ligand (FasL) and caspase-3 in renal tissue. Significance Telmisartan, through its antioxidant and anti-inflammatory actions, effectively prevented cadmium nephrotoxicity in mice. Hence, telmisartan represents a potential candidate to protect the kidney from the detrimental effect of cadmium toxicity.