Pharmacological influence on processes of adjuvant arthritis: effect of the combination of an antioxidant active substance with methotrexate

Abstract

Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis. A certain correlation was observed between oxidative stress, arthritis and the immune system. Reactive oxygen species produced in the course of cellular oxidative phosphorylation and by activated phagocytic cells during oxidative burst, exceed the physiological buffering capacity and result in oxidative stress. The excessive production of ROS can damage protein, lipids, nucleic acids, and matrix components. Patients with rheumatoid arthritis have an altered antioxidant defense capacity barrier. In the present study the effect of substances with antioxidative properties, i.e. pinosylvin and carnosine, was determined in monotherapy for the treatment of adjuvant arthritis (AA). Moreover carnosine was evaluated in combination therapy with methotrexate. Rats with AA were administered first pinosylvin (30 mg/kg body mass daily per os), second carnosine (150 mg/kg body mass daily per os) in monotherapy for a period of 28 days. Further, rats with AA were administered methotrexate (0.3 mg/kg body mass 2-times weekly per os), and a combination of methotrexate+carnosine, with the carnosine dose being the same as in the previous experiment. Parameters, i.e. changes in hind paw volume and arthritic score were determined in rats as indicators of destructive arthritis-associated clinical changes. Plasmatic levels of TBARS and lag time of Fe2+-induced lipid peroxidation (tau-FeLP) in plasma and brain were specified as markers of oxidation. Plasmatic level of CRP and activity of γ-glutamyltransferase (GGT) in spleen and joint were used as inflammation markers. In comparison to pinosylvin, administration of carnosine monotherapy led to a significant decrease in the majority of the parameters studied. In the combination treatment with methotrexate+carnosine most parameters monitored were improved more remarkably than by methotrexate alone. Carnosine can increase the disease-modifying effect of methotrexate treatment in rat AA.

Bioflavonoid Robinin from Astragalus falcatus Lam. Mildly Improves the Effect of Metothrexate in Rats with Adjuvant Arthritis

“…In earlier investigations, we demonstrated a positive agreement between the GGT activity in joint tissue and the hind paw volume of AA animals [46]. Correspondingly, as it is shown in Figure 4A, our previous results [37,45,46] are also in a good agreement with the current observation in changes of HPV (Figure 3).…”

“…The combination of MTX and RB had a significant effect in lowering the GGT activity in joints of animals (Figure 4A). The effectivity of MTX was marked also in studies with a similar setting and design of the experiment [37,45]. In earlier investigations, we demonstrated a positive agreement between the GGT activity in joint tissue and the hind paw volume of AA animals [46].…”

The Role of Oxidative Stress in Physiopathology and Pharmacological Treatment with Pro- and Antioxidant Properties in Chronic Diseases

“…Therefore, the control of lipoprotein levels through the administration of statins is one of the main management alternatives to reduce the risk of atherosclerosis [ 34 ]. Statins antagonize the activity of the enzyme hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase, decreasing the production of intracellular cholesterol and decrease of liver LDL receptors [ 35 ]. Statins show pleiotropic effects on endothelial function, inhibition of thrombus gene activity, the stability of atherosclerosis plaques, and decreased inflammation and OS [ 36 ].…”

Inhibition of Oxidative Stress in Brain During Rat Adjuvant Arthritis by Carnosine, Trolox and Novel Trolox-Carnosine

“…During the administration of CARN and CARN-T we did not observe side effects, thus this substances might be interesting also for patients with RA. Also our previous results report a safe use of natural substances with antioxidative properties for treatment of AA , Drafi et al 2012.…”