The present study was carried out to evaluate the effect of exogenously administered metallothionein (MT) to rats exposed to high cadmium levels. A total of 72 rats were used in the study. The animals were divided into three groups: controls, Cd administered, and Cd+MT. Cadmium was administered by subcutaneous injection of cadmium(II) chloride at a dose of 3.5 mg/kg for 7 d. In addition to CdCl2, 30 micromol/kg MT was administered to the second group of rats (group II). Control rats received 0.5 mL physiologic serum via subcutaneous injection. Eight rats from each group were sacrificed on the 1st, 3rd, 5th, and 7th day after administration of the compounds. Liver, kidney, and blood samples were harvested. Levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), serum ALT, AST, BUN, ALP, creatinine, and urea were measured. MDA levels in group I were observed to increase starting from d 1 compared to group II (p<0.05). Although MDA levels in group II were higher than controls (p<0.05), they were lower, especially in liver and blood, compared to group II. Erythrocyte GSH-Px activity levels were determined to decrease starting from d 1 in both groups (p<0.05). Decreases in GSH-Px activity levels in group II were less than group I. Serum creatinine levels in both groups were increased significantly compared to controls (p<0.05); the increase in group I was higher than group II. Serum ALT, AST, and ALP levels in group I increased to very high levels compared to controls, whereas increases in group II were at moderate levels (p<0.05). Although serum BUN levels were determined to be reduced, there was no significant change among the groups. Serum urea levels in both groups were higher than controls. Based on our results, it is possible to postulate that exogenous MT can act as antioxidant against Cd toxicity and lipid peroxidation.

The present study was performed to determine the protective effects of melatonin alone and vitamin E with selenium combination against cadmium-induced oxidative damage in rat liver. A total of 60 male rats were equally divided into five groups, one of which acted as control receiving subcutaneous injections of physiological saline. The remaining four groups were treated with subcutaneous injections of cadmium chloride at a dose of 1 mg/kg weight. The first study group received no treatment. The second group was treated with a combination of 60 mg/kg vitamin E and 1 mg/kg sodium selenite. Group 3 was treated with 10 mg/kg melatonin, and the four group received a combination of vitamin E, sodium selenite, and melatonin at the doses mentioned above. After 1 month, the animals were killed, and liver and kidneys were excised for histopathological inspection and determination of tissue malondialdehyde and the activity of superoxide dismutase. The animals receiving no treatment showed significantly higher malondialdehyde levels and reduced activity of superoxide dismutase (p < 0.05). Treatment with antioxidants resulted in a significant reduction in malondialdehyde when compared to nontreated animals (p < 0.05) and increase in the enzyme activity that was almost the same as the controls. The pathological findings were also in parallel with the results of the biochemical analysis. In conclusion, all the agents tested had protective effects against cadmium-induced oxidative damage.

No abstract

ÖzetMevcut araştırma; İsviçre Esmeri (İE), Holştayn (HOL), Simental (Sİ) ve Doğu Anadolu Kırmızısı (DAK) ırkı ineklerde prob ilaç olarak debrizokin (DEB) kullanılarak sitokrom P450 2D6 (CYP2D6) enzim aktivitesinin fenotipik belirlenmesi amacıyla yapıldı. Çalışmada her ırktan 15 adet olacak şekilde toplam 60 adet inek kullanıldı. İneklere DEB, 0.5 mg/kg dozunda uygulandı. Uygulamayı takiben 12 ve 24. saatlere kadar çıkarılan idrar örnekleri toplandı. İdrar örneklerinde DEB metabolik oranları (DMO) ve DEB rekoveri oranları (DRO) hesaplandı. 12. saat DMO değerleri DAK ırkı ineklerde diğer ırklara göre anlamlı şekilde yüksek olarak bulunurken (P<0.01), DRO değerleri DAK ırkı ineklerde diğer ırklara göre anlamlı şekilde düşük tespit edildi (P<0.01). DAK ırkı ineklerde CYP2D6 enzim aktivitesinin fenotipi zayıf metabolizer (ZM) olarak değerlendirilirken; İE, HOL ve Sİ ırkı ineklerde ise yaygın metabolizer (YM) olarak değerlendirildi. Sonuç olarak; ineklerde in vivo CYP2D6 enzim aktivitesi fenotipinin belirlenmesinde prob ilaç olarak DEB'in 0.5 mg/ kg dozunda uygulandıktan sonra 12. saatte kadar alınan idrar örneklerinin kullanılabileceği ifade edilebilir. Ayrıca, DAK ırkı ineklerde CYP2D6 sübstratı olan ilaçlarla tedavi uygulanmasında bu ilaçların daha yavaş metabolize olacağı, vücutta kalış ve etki sürelerinde artış olacağı sonucuna varılabilir. Anahtar sözcükler: CYP2D6, İnek, Debrizokin, Fenotiplendirme Phenotyping Determination of in vivo CYP2D6 Enzyme Activity Used as A Probe Debrisoquine in Swiss Black, Holstein, Simmental and Eastern Anatolian Red Cow Breeds SummaryIn the current study was carried out to determine phenotyping of in vivo CYP2D6 enzyme activity used as a probe debrisoquine (DEB) in Swiss Black (SB), Holstein (HOL), Simmental (SI) and Eastern Anatolian Red (EAR) cows. In the study, totally 60 cows, fifteen cows from each breed, were used. DEB was application at 0.5 mg/kg. Urine samples were collected throughout 12. and 24 th h after DEB application. The metabolic (DMR) and recovery (DRR) rates of DEB in urine samples were calculated to evaluate the in vivo activity of CYP2D6 enzyme activity. The DMR value of EAR at 12 th h were significantly higher than those others (P<0.01) while this value significantly lower in EAR compared to that of others (P<0.01). The phenotyping CYP2D6 enzyme activity of EAR at 12 th h was considered as poor metaboliser (PM) while this phenotype was extensive metabolizer (EM) in SB, HOL and SI cows. In conclusion, it can be considered that urine samples taken at 12 th h after DEB administration at dose of 0.5 mg/kg as probe can be used to determine in vivo phenotyping of CYP2D6 enzyme activity in cows. Besides, in implementation of treatment with drugs that are substrates of CYP2D6 in cows, it can be concluded that these drugs will be metabolized more slowly, and the duration time of body and effect durations of action will be increased in EAR cows.