Arginine administration reduces creatine kinase activity in rat cerebellum

Abstract

In the present study were evaluated the in vivo effects of arginine administration on creatine kinase (CK) activity in cerebellum of rats. We also tested the influence of antioxidants, namely alpha-tocopherol and ascorbic acid and the nitric oxide synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME), on the effects elicited by Arg in order to investigate the possible participation of nitric oxide (NO) and/or its derivatives peroxynitrite (ONOO(-)) and other/or free radicals on the effects of arginine on CK activity. Sixty-day-old rats were treated with a single i.p. injection of saline (control, group I), arginine (0.8 g/kg) (group II), L-NAME (2.0 mg/kg or 20.0 mg/kg) (group III) or Arg (0.8 g/kg) plus L-NAME (2.0 mg/kg or 20.0 mg/kg) (group IV) and were killed 1 h later. In another set of experiments, the animals were pretreated for 1 week with daily i.p. administration of saline (control) or alpha-tocopherol (40 mg/kg) and ascorbic acid (100 mg/kg). Twelve hours after the last injection of the antioxidants, the rats received one i.p. injection of arginine (0.8 g/kg) or saline and were killed 1 h later. Results showed that total and cytosolic CK activities were significantly inhibited by arginine administration in cerebellum of rats, in contrast to mitochondrial CK activity which was not affected by this amino acid. Furthermore, simultaneous injection of L-NAME (20.0 mg/kg) and treatment with alpha-tocopherol and ascorbic acid prevented these effects. The data indicate that the reduction of CK activity in cerebellum of rats caused by arginine was probably mediated by NO and/or its derivatives ONOO(-)and other free radicals. Considering the importance of CK for the maintenance of energy homeostasis in the brain, if this enzyme inhibition also occurs in hyperargininemic patients, it is possible that CK inhibition may be one of the mechanisms by which arginine is neurotoxic in hyperargininemia.

Impaired mitochondrial respiration and protein nitration in the rat hippocampus after acute inhalation of combustion smoke

“…Reduced activity of CK can reduce ADP supply to the mitochondrial ATP synthase and thereby compromise energy generation (Wallimann et al, 1998). The particular importance of CK in the brain, where energy demands may increase rapidly in health and pathology, has been recently described (Delwing et al, 2007; Andres et al, 2008). Interestingly, our earlier studies revealed elevation in the mitochondrial creatine kinase mRNA at 24 h after exposure to smoke (Lee et al, 2005), while here, we report that the protein becomes nitrated about the same time.…”

Guanidinoacetate Decreases Antioxidant Defenses and Total Protein Sulfhydryl Content in Striatum of Rats

“…It has been suggest that oxidative stress can to be involved in many disorders, including neurodegenerative, and metabolic diseases [24][25][26][27][28][29]. Oxidative stress can result from distinct situations, such as formation of free radicals at abnormally high rate, insufficient antioxidant defenses or due to a combination of these conditions [30].…”

Guanidino compounds inhibit acetylcholinesterase and butyrylcholinesterase activities: Effect neuroprotector of vitamins E plus C

“…It has been shown that Arg acute administration decreases the activities of the enzymes Na + ,K + ‐ATPase (Wyse et al, 2001a,b; Delwing et al, 2007a), AChE (Wyse et al, 2004), creatine kinase (Delwing et al, 2007b), CAT (Delwing et al, 2002) impairs respiratory chain (Delwing et al, 2003a,b, 2006), memory of rats (Reis et al, 2002), increases lipid peroxidation and decreases the nonenzymatic antioxidant defenses (Wyse et al, 2001a,b) and that intracerebroventricular administration of Arg increases TBA‐RS and decreases total radical‐trapping antioxidant parameter (TRAP) in cerebrum of rats (Delwing et al, 2007a). Such of these alterations were prevented by l ‐NAME, an inhibitor of nitric oxide synthase (Wyse et al, 2001a,b; Delwing et al, 2003a,b, 2007a,b) or α‐tocopherol plus ascorbic acid (Bavaresco et al, 2003; Wyse et al, 2004; Delwing et al, 2006, 2007a), suggesting that nitric oxide or free radicals are involved in such effects. Furthermore Arg administration also reduces ATP, ADP and AMP hydrolysis and BuChE activity in rat blood serum (Wyse et al, 2004; Delwing et al, 2005).…”