Does combined antioxidant vitamin supplementation blunt repeated bout effect?

We investigated the effect of antioxidant supplementation on markers of muscle damage, antioxidant status, and delayed onset of muscle soreness (DOMS) after repeated downhill runs. Moderately-trained males (n=22) were randomly assigned to a supplement (S) or placebo (P) group. Capsules (vitamin C:1 000 mg/d; vitamin E: 400 IU/d) were ingested daily for 2 weeks. before the first (1D) and second (2D) downhill runs, and for 2 additional days following each run. Creatine kinase (CK) activity and oxygen radical absorbance capacity (ORAC) were measured pre-exercise and at 0 (immediately), 6, 24 and 48 h post-exercise (POST). DOMS was rated for quadriceps, hamstring, gluteus, gastrocnemius, and tibialis anterior at 0, 24, 48 and 72 h POST. CK at 48 h following 1D remained elevated above pre-exercise only in P (P<0.01). Overall, DOMS of the quadriceps was lower in S (1.1±0.3) than P (2.2±0.5) (P<0.05). At 24 h POST in S, CK was lower (P<0.01) and ORAC was higher (P<0.05) following 2D than 1D. CK and ORAC following 2D were blunted and augmented, respectively, in response to 1D and antioxidant supplementation enhanced this protective effect as indicated by an attenuation of biomarkers of muscle damage and a greater antioxidant capacity observed 24 h POST 2D.

Nucleus accumbens and effort-related functions: behavioral and neural markers of the interactions between adenosine A2A and dopamine D2 receptors.

Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior and effort-related choice behavior. Moreover, there is evidence of an interaction between DA D(2) and adenosine A(2A) receptor function. Systemic administration of adenosine A(2A) antagonists reverses the effects of D(2) antagonists on tasks that assess effort related choice. The present experiments were conducted to determine if nucleus accumbens is a brain locus at which adenosine A(2A) and DA D(2) antagonists interact to regulate effort-related choice behavior. A concurrent fixed ratio 5 (FR5)/chow feeding procedure was used; with this procedure, rats can choose between completing an FR5 lever-pressing requirement for a preferred food (i.e., high carbohydrate operant pellets) or approaching and consuming a freely available food (i.e., standard rodent chow). Rats trained with this procedure spend most of their time pressing the lever for the preferred food, and eat very little of the concurrently available chow. Intracranial injections of the selective DA D(2) receptor antagonist eticlopride (1.0, 2.0, 4.0 microg) into nucleus accumbens core, but not a dorsal control site, suppressed FR5 lever-pressing and increased consumption of freely available chow. Either systemic or intra-accumbens injections of the adenosine A(2A) receptor antagonist MSX-3 reversed these effects of eticlopride on effort-related choice. Intra-accumbens injections of eticlopride also increased local expression of c-Fos immunoreactivity, and this effect was attenuated by co-administration of MSX-3. Adenosine and DA systems interact to regulate instrumental behavior and effort-related processes, and nucleus accumbens is an important locus for this interaction. These findings may have implications for the treatment of psychiatric symptoms such as psychomotor slowing, anergia and fatigue.

Synthetic 2-aroylindole derivatives as a new class of potent tubulin-inhibitory, antimitotic agents.

A new class of simple synthetic antimitotic compounds based on 2-aroylindoles was discovered. (5-Methoxy-1H-2-indolyl)-phenylmethanone (1) as well as analogous 3-fluorophenyl- (36) and 3-methoxyphenyl (3) derivatives displayed high cytotoxicity of IC(50) = 20 to 75 nM against the human HeLa/KB cervical, SK-OV-3 ovarian, and U373 astrocytoma carcinoma cell lines. The inhibition of proliferation correlated with the arrest in the G2/M phase of the cell cycle. In in vitro assays with tubulin isolated from bovine brain, in general antiproliferative activity correlated with inhibition of tubulin polymerization. Thus, the antimitotic activity of 2-aroylindoles is explained by interference with the mitotic spindle apparatus and destabilization of microtubules. In contrast to colchicine, vincristine, nocodazole, or taxol, 1 did not significantly affect the GTPase activity of beta-tubulin. Interestingly, selected compounds inhibited angiogenesis in the chorioallantoic membrane (CAM) assay. In xenograft experiments, 1 was highly active after oral administration at 200 mg/kg against the human amelanocytic melanoma MEXF 989 in athymic nude mice. We conclude, that 2-aroylindoles constitute an interesting new class of antitubulin agents with the potential to be clinically developed for cancer treatment.