Alpha-lipoic acid could be a promising treatment in steroid-induced osteonecrosis.

OBJECTIVE: Glucocorticoid-induced osteonecrosis is a serious debilitating health problem. In the present study, we investigated the effects of alpha-lipoic acid on glucocorticoid-induced osteonecrosis in rats. MATERIALS AND METHODS: A total of 40 male Wistar albino rats were equally assigned to 4 groups as control, methylprednisolone acetate (MPA), alpha-lipoic acid (ALA), and methylprednisolone acetate with alpha-lipoic acid (MPA+ALA). The animals in MPA group subcutaneously received 15 mg/kg/week for 2 weeks, whereas 100 mg/kg/day alpha-lipoic acid was intraperitoneal administered for 4 weeks to ALA group. The MPA+ALA group was subjected to both treatments in same doses. Osteonecrosis was confirmed and graded histologically. The serum concentrations of glucose, total cholesterol, low- and high-density lipoprotein, triglyceride, as well as the total oxidant and antioxidant status, oxidative stress index, prothrombin time and activated partial thromboplastin time were evaluated. Also, lipid peroxidation and DNA damage were immunohistochemically assessed in the bone. RESULTS: Osteonecrotic lesions were narrower in the MPA+ALA group than in the MPA group (p<0.05). As compared to the controls, the biochemical parameters in MPA and MPA+ALA groups were significantly increased (p<0.001). The oxidative stress index was significantly higher in the groups with MPA than the controls (p=0.002), but the animals treated with ALA alongside MPA displayed lesser scores than the ones injected with solely MPA (p=0.03). The administration of MPA elevated lipid peroxidation and DNA damage, which were successfully alleviated by ALA. CONCLUSIONS: Alpha-lipoic acid may be suggested to be a protective supplement in glucocorticoid-induced osteonecrosis in rats. The antioxidant capacity of alpha-lipoic acid may involve its beneficial effects.

Methylprednisolone acetate mitigates IL1ß induced changes in matrix metalloproteinase gene expression in skeletally immature ovine explant knee tissues.

OBJECTIVE AND DESIGN: This study aimed at evaluating the effect of methylprednisolone (MPA) on messenger ribonucleic acid (mRNA) expression levels in immature ovine knee joint tissue explants following interleukin (IL)1ß induction and to assess responsiveness of the explants. MATERIAL OR SUBJECTS: Explants were harvested from the articular cartilage, synovium, and infrapatellar fat pad (IPFP) from immature female sheep. TREATMENT: Methylprednisolone. METHODS: The samples were allocated into six groups: (1) control, (2) MPA (10-3 M), (3) MPA (10-4 M), (4) IL1ß, (5) IL1ß + 10-3 M MPA, or (6) IL1ß + 10-4 M MPA. mRNA expression levels for molecules relevant to inflammation, cartilage degradation/anabolism, activation of innate immunity, and adipose tissue/hormones were quantified. Fold changes with MPA treatment were compared via the comparative CT method. RESULTS: Methylprednisolone treatment significantly suppressed MMPs consistently across the cartilage (MMP1, MMP3, and MMP13), synovium (MMP1 and MMP3), and IPFP (MMP13) (all p < 0.05). Other genes that were less consistently suppressed include endogenous IL1ß (cartilage) and IL6 (IPFP) (all p < 0.05), and others not affected either by IL-1 exposure or subsequent MPA include TGFß1, TLR4, and adipose-related molecules. CONCLUSIONS: Methylprednisolone significantly mitigated IL1ß induced mRNA expression for MMPs in the immature cartilage, synovium, and IPFP, but the extent of the responsiveness was tissue-, location-, and gene-specific.

Effect of intrathecal glucocorticoids on the central glucocorticoid receptor in a rat nerve ligation model.

BACKGROUND AND AIMS: Despite widespread use, the efficacy of neuraxial glucocorticoids for neuropathic pain is subject to debate. Since most glucocorticoid actions are mediated through its receptor, we explored the effects of intrathecal methylprednisolone acetate (MPA) on total glucocorticoid receptor (tGR) levels and activation of the glucocorticoid receptor (phosphorylated state=pGR) within the spinal dorsal horn (SDH) and dorsal root ganglion (DRG) in a spinal nerve ligation (SNL) model in rats. METHODS: Rats received unilateral ligation of the L5/L6 spinal nerves and were treated with two intrathecal doses of either 400µg MPA or 0.9% saline with a 72-h interval. Plantar tactile thresholds were measured over time. Seven days after drug treatment, DRG and SDH were harvested to assess tGR and pGR levels using immunohistochemistry and qPCR. RESULTS: Allodynia, defined by lowered tactile withdrawal thresholds after SNL, was unaltered by intrathecal MPA. In saline controls, mRNA levels of tGR did not change after SNL in the DRGs or SDH. tGR and pGR protein levels in the SDH however, significantly increased on the ipsilateral side of SNL compared to the contralateral side and to naïve tissue. When treating rats with MPA, tGR mRNA levels were significantly reduced in the SDH compared to saline controls. tGR and pGR protein levels, however were not significantly lower compared to saline controls. CONCLUSIONS: In intrathecal MPA treated rats, tGR mRNA levels decreased after SNL. However this did not result in lower tGR and pGR protein levels compared to saline controls, and did not decrease ligation-induced mechanical hypersensitivity. IMPLICATIONS: Intrathecal MPA treatment after SNL did not result in lower tGR and pGR levels within the SDH and DRG compared to saline controls. In present study we did not differentiate between the various isoforms of the GR which might clarify this finding.