No drug therapy has demonstrated improved survival following cardiac arrest (CA) of cardiac or noncardiac origin. In an effort to translate the cardiorescue properties of Adenocaine (adenosine and lidocaine) and magnesium sulfate (ALM) from cardiac surgery and hemorrhagic shock to resuscitation, we examined the effect of ALM on hemodynamic rescue and coagulopathy following asphyxial-induced CA in the rat. Nonheparinized animals (400-500 g, n = 39) were randomly assigned to 0.9% saline (n = 12) and 0.9% saline ALM (n = 10) groups. After baseline data were acquired, the animal was surface cooled (33°C-34°C) and the ventilator line clamped for 8 min inducing CA; 0.5 mL of solution was injected intravenously followed by 60-s chest compressions (300/min), and rats were rewarmed. Return of spontaneous circulation (ROSC), mean arterial pressure, heart rate, and rectal temperature were recorded for 2 h. Additional rats were randomized for rotation thromboelastometry measurements (n = 17). Rats treated with ALM had a significant survival benefit (100% ALM vs. 67% controls achieved ROSC) and generated a higher mean arterial pressure than did controls after 75 min (81 vs. 72 mmHg at 120 min, P < 0.05). In all rats, rotation thromboelastometry lysis index decreased during CA, implying hyperfibrinolysis. Control ROSC survivors displayed hypocoagulopathy (prolonged EXTEM/INTEM clotting time, clot formation time, prothrombin time, activated partial thromboplastin time), decreased maximal clot firmness, lowered elasticity, and lowered clot amplitudes but no change in lysis index. These coagulation abnormalities were corrected by ALM at 120 min after ROSC. Small bolus of 0.9% NaCl ALM improved survival and hemodynamics following nonhemorrhagic, asphyxial CA and corrected prolonged clot times and clot retraction compared with controls.

The use of the chemotherapy agent doxorubicin (DOX) is associated with free radical formation that may lead to cardiotoxicity. Virgin coconut oil (VCO) and extra virgin olive oil (EVOO) are plant-based oil that is rich in antioxidants. This study examined the protective effects of VCO and EVOO combination to reduce DOX acute cardiotoxicity in rats. Twenty-five male rats (180-200 g) were divided into the following groups: Group I as a control, group II was given DOX i.p. injection of 25 mg/kg body weight (b.w.), group III to V received peroral administration of either VCO, EVOO or VCO-EVOO (1:1) combination at a dose of 10 mL/kg b.w. for 6 days before receiving DOX i.p. injection. After 24 hours from DOX injection, blood samples and organs were collected. Cardiac biomarkers, such as serum glutamic-oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), and creatine kinase-MB (CKMB) were analyzed followed by histopathological examination. The administration of EVOO alone was found to reduce the marked elevation of SGOT, LDH, and CKMB levels in DOX-treated rats (p<0.05), while VCO administration only significantly reduced LDH and CKMB levels. However, when both oils were used in combination, the protective effect was shown to be more powerful since all cardiac biomarker levels were maintained at near-normal levels (p<0.05). Histopathological analysis showed a significant improvement in the myocardial tissue structures after pre-treatment with VCO-EVOO combination. The administration of VCO and EVOO in combination was superior to elicit protection against DOX-induced cardiotoxicity compared to their individual application in rats.

Doxorubicin (DOX) is a potent chemotherapy agent; however, its use may lead to cardiac, hepatic, and renal dysfunction. Kleinhovia hospita L extract contains antioxidant compounds that have been shown to reduce chemical-induced hepatotoxicity. This study aimed to examine the protective effects of Kleinhovia sp. extract to reduce DOX acute toxicities. Thirty male rats were assigned to the following groups: Group I as controls, Group II was given DOX i.p. injection (25 mg/kg); Groups III, IV, and V were treated with Kleinhovia sp. extract 100, 250, and 500 mg/kg orally for 5 days, respectively, prior to DOX i.p. injection. After 24 h, blood and organs were analyzed for biomarker levels and histopathological changes. DOX treatment in Group II significantly increased creatine kinase-MB (CK-MB), aspartate transaminase (AST), alanine transaminase (ALT), and urea levels compared to controls. Kleinhovia sp. extract at any given dose significantly improved ALT and AST; yet, CK-MB levels only reduced with 250 mg/kg dose (Group IV). Urea and creatinine levels in Kleinhovia sp. groups were also lower compared to DOX-treated rats, but it was not significant. Histopathological analysis showed improved liver, heart, and renal tissue structures in Kleinhovia sp-treated rats, especially at higher doses. Kleinhovia sp. extract at any dose given protected the rats from liver toxicity, but only at dose 250 mg/kg reduced cardiac toxicity. Although renal biomarkers were insignificantly lower, renal architecture was improved with Kleinhovia sp. treatment. Doxorubicin (25 mg/kg) i.p injection led to elevated ALT, AST, CK-MB and urea levels in rats.At the given dose, doxorubicin induced pathological changes in cardiac, liver and renal tissues.Pretreatment with Kleinhovia sp. extract prior to doxorubicin injection significantly reduced the elevation of ALT, AST and CK-MB, especially at the dose of 250 mg/kg.Improvement in histological structures of cardiac, liver and renal tissues was shown in Kleinhovia sp. (250 mg/kg) treated rats, indicating a protective effect of the extract on doxorubicin acute toxicity. Abbreviations Used: DOX: Doxorubicin; CK-MB: creatine kinase-MB, AST: Aspartate transaminase; ALT: Alanine transaminase

Background: Levofloxacin is a fluoroquinolone antibiotic that has broad-spectrum antimicrobial activity, but it may induce kidney dysfunction. Clove oil (Oleum caryophylli) has antioxidant properties that may alleviate levofloxacin toxicity. This study aimed to examine the protective effect of clove oil on levofloxacin-induced nephrotoxicity in rat animal models. Methods: A total of 24 male rats were divided into 6 groups. One group did not receive levofloxacin to serve as the control. The treatment groups received a single daily administration of levofloxacin (93 mg/kg) with either placebo or clove oil (10 mg/kg, 25 mg/kg, or 50 mg/kg per body weight) pre-treatment. Another group received Curcuma extract pre-treatment as a comparison. Blood samples were withdrawn after 28 days of treatment to measure serum biomarkers (urea and creatinine), and the kidneys were removed to measure renal Malondialdehyde (MDA) and histopathological analysis. Results: The results showed that clove oil pre-treatment at a dose of 10 mg/kg was able to reduce renal MDA and serum biomarker levels (P<0.05). The effect was similar to that found in Curcuma-treated rats. In addition, clove oil (10 mg/kg) was also found to ameliorate renal histopathological damage due to levofloxacin. Conclusion: Based on biomarker and histopathological analysis, clove oil pre-treatment in rats provides a nephroprotective effect against levofloxacin toxicity.

Introduction: Antituberculosis drugs are associated with hepatic and renal toxicities due to drug’s radical metabolites. Kleinhovia hospita L extract possesses a potent antioxidant capacity that can be beneficial in eradication of oxidative-induced cell damage. This study aimed to evaluate the effects of K. hospita hydro-alcoholic extract on biomarkers and structure changes in liver and kidney induced by a combination of antituberculosis drugs (CAD), comprising isoniazid, rifampicin, pyrazinamide and ethambutol in Wistar rats. Methods: Thirty-five male Wistar rats were assigned into one of the five groups: control, CAD, and CAD with K. hospita extract in three different doses (125, 250 and 500 mg/kg). The extract was administered three hours prior to CAD and all treatments were carried out for 28 days. Following the last day of treatment, blood samples and organs were collected for biomarker analysis and histopathological examinations. Results: Twenty-eight days of CAD treatment in rats induced marked elevation of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum creatinine and urea levels compared to controls. K. hospita extract at higher doses (250 mg/kg and 500 mg/kg) significantly improved ALT, urea and creatinine levels in the rats treated with CAD (P<0.05), although it did not significantly reduce AST. Furthermore, liver and renal tissue damages induced by CAD were restored with K. hospita extract treatment, especially at higher doses. Conclusion: Kleinhovia hospita extract treatment has the potential to protect the liver and renal damage induced by toxic doses of CAD.