Effect of doxycycline and meloxicam on cytokines, brain-derived neurotrophic factor, matrix metalloproteinase-3, tissue inhibitor of metalloproteinase-3 and cyclooxygenase-2 in brain

强力霉素和美洛昔康对脑细胞因子、脑源性神经营养因子、基质金属蛋白酶-3、组织金属蛋白酶抑制剂-3和环氧合酶-2的影响

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作者:Ayse Er, Devran Coskun, Emre Bahcivan, Burak Dik

Conclusion

DOX or MLX monotherapy exerts neuroprotective effects against brain inflammation by decreasing proinflammatory cytokine levels and by increasing anti-inflammatory cytokines levels.

Methods

Seventy-eight rats were divided into the following groups: control (n=6), LPS (0.5 μg/10 μl intracranial) (n=18), LPS (0.5 μg/10 μl intracranial)+DOX (40 mg/kg intraperitoneal) (n=18), LPS (0.5 μg/10 μl intracranial)+MLX (2 mg/kg intraperitoneal) (n=18) and LPS (0.5 μg/10 μl intracranial)+DOX (40 mg/kg intraperitoneal)+MLX (2 mg/kg intraperitoneal) (n=18) groups. Brain tissues were harvested from all rats in the control group and from six rats each in the four experimental groups at 1, 3 and 6 hr under anaesthesia. The levels of tumor necrosis factor α (TNFα), interleukin 4 (IL-4), IL-6, IL-10, IL-17, brain-derived neurotrophic factor (BDNF), matrix metalloproteinase 3 (MMP-3), tissue inhibitor of metalloproteinase 3 (TIMP-3) and cyclooxygenase 2 (COX-2) in the brain tissues were measured using ELISA kits with ELISA device.

Results

LPS administration increased proinflammatory cytokines (TNF, IL-6, IL-17), and MMP-3 levels and decreased anti-inflammatory cytokines (IL-10, IL-4), and BDNF levels. The lowest TNFα levels were detected in the LPS+MLX group (P<0.05). All the drug treatment groups showed decreased IL-17 and COX-2 levels compared to the LPS groups.

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