Therapeutic Effects of the Superoxide Dismutase Mimetic Compound Me₂DO2A on Experimental Articular Pain in Rats

Abstract

Superoxide anion (O2 •−) is overproduced in joint inflammation, rheumatoid arthritis, and osteoarthritis. Increased O2 •− production leads to tissue damage, articular degeneration, and pain. In these conditions, the physiological defense against O2 •−, superoxide dismutases (SOD) are decreased. The MnII complex MnL4 is a potent SOD mimetic, and in this study it was tested in inflammatory and osteoarticular rat pain models. In vivo protocols were approved by the animal Ethical Committee of the University of Florence. Pain was measured by paw pressure and hind limb weight bearing alterations tests. MnL4 (15 mg kg−1) acutely administered, significantly reduced pain induced by carrageenan, complete Freund's adjuvant (CFA), and sodium monoiodoacetate (MIA). In CFA and MIA protocols, it ameliorated the alteration of postural equilibrium. When administered by osmotic pump in the MIA osteoarthritis, MnL4 reduced pain, articular derangement, plasma TNF alpha levels, and protein carbonylation. The scaffold ring was ineffective. MnL4 (10−7 M) prevented the lipid peroxidation of isolated human chondrocytes when O2 •− was produced by RAW 264.7. MnL4 behaves as a potent pain reliever in acute inflammatory and chronic articular pain, being its efficacy related to antioxidant property. Therefore MnL4 appears as a novel protective compound potentially suitable for the treatment of joint diseases.

Effect of the SOD mimetic MnL4 on in vitro and in vivo oxaliplatin toxicity: Possible aid in chemotherapy induced neuropathy

“…MnL4 ameliorates lung inflammation, oxidative injury and breathing dysfunction induced by exposure to the air-borne allergen in sensitized guinea pigs [17]. The molecule administered both acutely at the dose of 15 mg kg À 1 or by osmotic pump (15 mg kg À 1 die for 14 days, chronic slow release) largely reduces neuropathic and inflammatory pain in different models of osteoarthritis and rheumatoid arthritis [18]. Moreover, the efficacy of SOD-mimetic compounds was also described in animal models of inflammatory and neuropathic pain [19].…”

Effects of Gc-Macrophage Activating Factor in Human Neurons; Implications for Treatment of Chronic Fatigue Syndrome

“…On day 0, rats were slightly anesthetized by 2% isoflurane, the left leg skin was sterilized with 75% ethyl alcohol and the lateral malleolus located by palpation; then, a 28-gauge needle was inserted vertically to penetrate the skin and turned distally for insertion into the articular cavity at the gap between the tibiofibular and tarsal bone until a distinct loss of resistance was felt. MIA dose of 2 mg in 25 µL saline was delivered into the left articular cavity (Mannelli et al, 2013). The paw pressure tests (see below) were performed at day 14.…”

“…at day 14. The pain threshold in the rat was determined with an analgesimeter (Ugo Basile, Varese, Italy) as described (Mannelli et al, 2013). Briefly, a constantly increasing pressure was applied to a small area of the dorsal surface of the paw using a blunt conical probe (Fig.…”

“…Therefore, having observed a significant stimulatory effects of GcMAF on mitochondrial activity in human neurons (Fig. 2), we decided to study its effects in a well-established model of inflammatory pain that is the osteoarthritic pain induced by MIA (Mannelli et al, 2013). It is well assessed that morphological alterations are associated with a persistent inflammatory pain which, starting from the 14th day after MIA injection, possesses a neuropathic component (Ivanavicius et al, 2007).…”

Effects of a water extract of Lepidium meyenii root in different models of persistent pain in rats

“…Moreover, maca improves the antioxidant cell machinery [19]. Cannabinoid and cholinergic systems [20,21], as well as redox unbalance [22][23][24][25], play a relevant role in persistent pain processes. Maca consumption has been associated with lower serum levels of the proinflammatory and proalgic cytokine IL-6 in populations living in the Peruvian Central Andes [8].…”