Thymus oil and its components are becoming increasingly popular as naturally occurring antimicrobial and antioxidant agents. The real importance of thymus on nitric oxide (NO) is unknown. NO is an important mediator in numerous physiologic and pathophysiologic events. Stasis and thrombosis in burn wound can progress as a result of the release of local mediators. The implication of NO in burn injury is not well studied. In this study, we tried to determine the role of burn-induced NO and whether thymus oil plays a protective role after a thermal injury. Rats were divided into five groups. We topically applied thymus oil, olive oil, and silverdin and sulfadiazine on the rats, respectively, during a period of 21 days after they were burned while under anesthesia. The burned control group and nonburned control group did not receive any treatment. The results of this study show that NO was overproduced by thermal injury and decreased during the days after burn injury. The decrease in rats treated with thymus and sulfadiazine was higher than the others. These data indicate that thymus oil may serve as a protective agent to the damaged tissues by decreasing the NO level. Histologic examination results show that the formation of new tissue in rats receiving thymus oil was more than other burned groups, and this finding supports our hypothesis.

The results of experiments designed to show that inhibition of nitric oxide production in rats exposed to low lead levels increases vascular resistance, decreases renal blood flow and glomerular function, and enhances oxidative stress. Forty-five adult male Sprague-Dawley rats were divided into four groups. Group A was used as controls and consisted of rats that received no treatment; group B acted as NO-inhibited controls by receiving L-NAME (N(G)-nitro-l-arginine methyl ester) as the NO inhibitor; group C was injected intraperitoneally with 8 mg/kg lead acetate for 2 wk; and group D receiving lead acetate plus L-NAME. Compared to healthy controls, significant elevation of the mean (p<0.01), systolic (p<0.04), and diastolic (p<0.01) blood pressures was found in the lead-treated rats. The renal blood flow was 1550+/-468 blood per unit (bpu) in the controls, 488+/-220 bpu in the L-NAME controls, 1050+/-458 bpu in the lead-treated group, and 878+/-487 bpu in the Pb plus L-NAME group. Low-level lead exposure did not change the urinary flow rate, creatinine clearance, and the creatinine, potassium, phosphorus, glucose, and protein excretion in 24-h urine. In the lead plus NO-inhibited rats, a significant decrease in sodium ion excretion was observed (p<0.01). The NO levels of the lead exposed, L-NAME-treated controls, and L-NAME plus lead-exposed groups are significantly lower compared to untreated controls: p<0.002, p<0.001, and p<0.01, respectively. When compared to untreated controls, the plasma malondialdehyde levels were not significantly different in the lead exposed, lead plus L-NAME, and L-NAME control groups. These results suggest that lead-induced hypertension might be related to a decrease of NO and consequent vasoconstriction, rather than to a decrease of renal blood flow or to decreases in renal sodium.

ÖZETAmaç: Oksidatif stres, adriamisinin (ADR) neden olduğu kardiyak fonksiyon bozukluğu patogenezinde, önemli faktörlerden birisidir. Bu çalışma-da sıçanlarda adriamisin ile oluşturulan kalp hasarı üzerine karnozinin antioksidan savunma etkisi araştırılmıştır. Yöntemler: Dişi Spraque Dawley sıçanlar 4 gruba ayrıldı; kontrol (KONT, n=8, serum fizyolojik i.v.); karnozin (KAR, n=8, 10 mg/kg/gün, i.v.) sadece adriamisin (ADR, n=10, 4 mg/kg dört defa, iki gün ara ile toplam 8 gün, i.v.); karnozin ile adriamisin (KAR+ADR, n=10). Karnozin, adriamisinden bir hafta önce verilmeye başlandı ve sonraki bir hafta adriamisinle birlikte verildi. Fizyolojik fonksiyon değerlendirmelerinden sonra biyokimyasal tayinler için kan örnekleri alındı. Kalpler hemodinamik çalışma için izole edildi. Gruplar arası farklılıkların belirlenmesi için ANOVA ve posthoc Tukey testi kullanıldı. Bulgular: Adriamisin, belirgin bir şekilde kalp hasarı yapmış olup; karnozin ve kontrol grubuna göre, hemodinamik değişiklikler [azalmış sol ventrikül basınç gelişimi (p<0.01), maksimum-minimum sol ventrikül basınç değişim oranları (±dP/dt, p<0.01)], elektrokardiyogram (EKG) değişik-likleri (artmış ST ve azalmış R-dalgası, p<0.001), kardiyak hasar belirleyicilerindeki değişiklikler (artmış kreatin kinaz, laktat dehidrogenaz, aspartat aminotransferaz, alanin aminotransferaz), plazma antioksidan aktivite değişiklikleri (azalmış süperoksit dismutaz, glutatyon peroksidaz, katalaz aktiviteleri, p<0.03) ve lipit peroksidasyonuna (artmış malondialdehit, p<0.05) neden olmuştur. Karnozin tedavisi (KAR+ADR); ventriküler ABSTRACT Objective: Oxidative stress is one of the major factors involved in the pathogenesis of adriamycin (ADR)-induced cardiac dysfunction. The present study examined the antioxidant protective effects of carnosine (CAR) on adriamycin-induced cardiac damage in rats. Methods: Female Sprague Dawley rats were divided into four groups. Control (CONT, n=8, saline only i.v.); carnosine (CAR, n=8.10 mg/kg/day, i.v.); adriamycin (ADR, n=10.4 mg/kg four times every 2 days for 8 days, i.v.) alone and carnosine with adriamycin (CAR+ADR, n=10). Carnosine was given one week before adriamycin treatment and following one week with adriamycin treatment. After measurement of physiological functions, blood samples were collected for biochemical assays. The hearts were excised for hemodynamic study. Comparisons between different groups were made using ANOVA and posthoc Tukey test. Results: Adriamycin produced evident cardiac damage revealed by; hemodynamic changes -decreased left ventricular developed pressure (p<0.01), the maximum-minimum rates of change in left ventricular pressure (±dP/dt, p<0.01), electrocardiogram (ECG) changes (elevated ST, decreased R-wave, p<0.001), cardiac injury marker changes (increased creatine kinase, lactate dehydrogenase, aspartate aminotransferase and alanine aminotransferase), plasma antioxidant enzymes activity changes (decreased superoxide dismutase, glutathione peroxidase, catalase activities, p<0.03) and lipid peroxidation (eleva...

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Although adriamycin (ADR) exhibits high anti-tumor efficacy in vitro, its clinical use in cancer chemotherapy is limited due to its high renal toxicity. This study investigated the mechanism of ADR nephropathy and the protective effect of selenium on ADR-induced kidney damage by analyzing of the relationship between selenium and mitochondria. Rats were divided into four groups. The first group was injected with saline i.p. for 21 days, the second group received the 4 mg/kg i.p. ADR every alternate day for 8 days, the third group received the 50 μg/kg i.p. Se for 21 days, and the fourth group received the Se. ADR co-administration i.p. blood pressures were assessed, the mitochondrial membrane potential (MMP) was assessed, and the adenosine triphosphate (ATP) levels were determined. The total antioxidant (TAS) and oxidant status (TOS) in cytosol, the mitochondria of kidney cells, and plasma were measured. Mitochondrial TAS decreased and TOS increased in the ADR group compared to the Se group. ADR-treated rats showed significantly lower MMP than did the control and Se groups. MMP was significantly restored in the Se + ADR group through selenium treatment compared to the ADR group (p < 0.01). In the ADR group, a reduction in ATP content was seen compared to the control and Se groups (p < 0.01). ATP level was significantly restored through treatment with selenium in the Se + ADR group compared to the ADR group (p < 0.01). We concluded that selenium is effective in vivo against ADR-induced kidney damage via the restoration of TAS and TOS, which prevented mitochondrial damage.

Adriamycin (ADR) is commonly used for many solid tumor treatments. Its clinical utility is, however, largely limited by the adverse reactions, are known to be nephrotoxic. The mechanism by which it induces kidney damage is still not completely understood, but its nephrotoxicity might relate to increase reactive oxidant status (ROS), mitochondrial dysfunction. Until now, neurohormonal activation of it is unclear. ADR might activate the renin angiotensin system. Angiotensin-II also induced ROS and mitochondrial dysfunction. The aim of this study was to investigate whether angiotensin-II production inhibition has the protective effect on attenuation of mitochondrial function in rats with acute ADR-nephrotoxicity or not. Rats were divided into five groups as a control, ADR, co-treated ADR with captopril (CAP), co-treated ADR with Aliskren, co-treated ADR with both CAP and Aliskren groups. Creatinine kinase (CK) levels were measured at the end of treatment period. The kidneys were homogenized and biochemical measurements were made in mitochondria, cytosol. Mitochondria membrane potential (MMP) and ATP levels were determined. ADR increased CK levels and oxidative stress in mitochondria too (p50.05). ADR significantly decreased MMP and ATP level in kidney mitochondria (p50.05). Co-administration with ADR and Aliskren and CAP improved the dissipation of MMP (p50.05). The decrease in ATP level was restored by treatment with inhibitors of ACE and renin. We concluded that inhibitors of angiotensin-II are effective against acute ADR induced nephrotoxicity via the restoration of MMP and ATP production and prevention of mitochondrial damage in vivo. KeywordsAdriamycin-induced nephrotoxicity, Aliskren, captopril, mitochondrial ATP, mitochondrial membrane potential, oxidative stress index History

Adriamycin (ADR) causes morphological and functional alterations in mitochondrial structure in the heart. The study's aim was to determine whether there is a protective effect of selenium (Se) on ADR-induced cardiac damage. Rats were divided into four groups: The first group was injected saline intraperitoneally (i.p.) for 21 days; the second group received 4 mg/kg i.p. ADR every alternate day for 8 days; the third group received 50 µg/kg i.p. Se for 21 days; and the fourth received the Se (for 21 days) and ADR (for 8 days) coadministration i.p. Left ventricular functions, electrocardiography parameters, and blood pressures were assessed. Mitochondrial membrane potential (MMP), adenosine triphosphate (ATP) level, and thioredoxin reductase (TrxR) activity were determined. Total antioxidant (TAS) and oxidant status (TOS) in cytosol, mitochondria of myocytes, and plasma were measured. Left ventricular data demonstrated left ventricular systolic pressure (LVSP) decreased, left ventricular developed pressure (LVDP) decreased, and left ventricular end-diastolic pressure (LVEDP) increased in ADR-treated animals, compared to the control and Se groups. ADR decreased the membrane potential and ATP level in myocyte mitochondria. TrxR activity decreased in the ADR group, compared to the Se group. Cytosolic and mitochondrial TAS decreased and mitochondrial and plasma TOS increased in the ADR group, compared to the control. The coadministration of Se with ADR attenuated left ventricular dysfunction, improved MMP and ATP levels, and prevented oxidative stress by increasing antioxidants (especially TrxR) and decreasing oxidants. We concluded that Se is effective against ADR-induced cardiac damage via the restoration of TAS and TOS, which prevented mitochondrial damage.

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