The effect of L-Arginine from Giant Snake Head fish (Channa micropeltes) on neuroinflammation and neuron damage in traumatic brain injury in rats

Andy Nugroho, D. Tamtomo, D. Indarto, R. Cilmiaty, Soetrisno
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Abstract

Backgrounds: Traumatic brain injury has high mortality and morbidity. The involvement of neuroinflammatory responses and neuronal damage in traumatic brain injury is the basis for the development of renewable neuroprotective agents, one of which is the amino acid L-Arginine. The amino acid L-Arginine which can be found in Giant Snake Head fish (Channa micropeltes) is thought to inhibit anti-inflammatory effects through the Arg-1 signaling pathway. Aims: To prove and analyze the effect of giving L-Arginine Giant Snake Head fish on neuroinflammation and neuronal damage in a rat model of traumatic brain injury. Methods: This randomized controlled trial (RCT) study used a posttest-only control group design. Thirty-five male rats (Rattus norvegicus) with the Wistar strain were randomly divided into five treatment groups, namely the normal control group (N), negative control (KN), and 3 treatment groups (A-C). The KN and A-C groups were modeled after traumatic brain injury and given L-Arginine at a dose of 0.5; 1.5; and 3 g/kgBW/day for 7 days specifically A-C. Brain tissue samples were used for the examination of TLR4, TNF-α, GSDMD, Caspase-3, and histopathological features. All data were analyzed using the Kruskall-Wallis test, except for GSDMD expression with a significance <0.05. Results: The mean TLR4 expression in A (15.7 ± 5.35), B (12.9 ± 5.67), and C (11.4 ± 6.27) were lower and significant compared to KN, but higher and significant compared to N. The same pattern appears in the decrease in TNF-α expression, Caspase-3 expression, and histopathology of brain tissue damage. The mean relative expression of GSDMD to N in A (1.3 ± 0.53), B (1.2 ± 0.52), and C (1.2 ± 0.60) was higher than in KN, but not significant. Relative expression of GSDMD to Beta Actin, A and B have the same higher expression than C, KN, and N. Conclusion: Expression of TLR-4, TNF-α, Caspase-3 and histopathology of brain tissue damage in traumatic brain injury model rats given Giant Snake Head fish L-Arginine were lower than without L-Arginine. Meanwhile, the expression of GSDMD in traumatic brain injury model rats when given Giant Snake Head fish L-Arginine was slightly higher than without L-Arginine.
从巨蛇头鱼(Channa micropeltes)中提取的 L-精氨酸对脑外伤大鼠神经炎症和神经元损伤的影响
背景:创伤性脑损伤的死亡率和发病率都很高。创伤性脑损伤涉及神经炎症反应和神经元损伤,这是开发可再生神经保护剂的基础,L-精氨酸氨基酸就是其中之一。巨蛇头鱼(Channa micropeltes)中含有的氨基酸 L-精氨酸被认为可通过 Arg-1 信号通路抑制抗炎作用。目的:证明并分析给予巨蛇头鱼 L-Arginine 对创伤性脑损伤大鼠模型中神经炎症和神经元损伤的影响。方法:随机对照试验(RCT):本随机对照试验(RCT)研究采用仅试验后对照组设计。35 只 Wistar 品系雄性大鼠(Rattus norvegicus)被随机分为 5 个治疗组,即正常对照组(N)、阴性对照组(KN)和 3 个治疗组(A-C)。KN组和A-C组在脑外伤后进行建模,并以0.5、1.5和3克/千克体重/天的剂量连续7天服用精氨酸。脑组织样本用于检测 TLR4、TNF-α、GSDMD、Caspase-3 和组织病理学特征。除 GSDMD 表达的显著性<0.05 外,所有数据均采用 Kruskall-Wallis 检验进行分析。结果与 KN 相比,A(15.7 ± 5.35)、B(12.9 ± 5.67)和 C(11.4 ± 6.27)中 TLR4 的平均表达量较低且显著,但与 N 相比,TLR4 的平均表达量较高且显著。在 A(1.3 ± 0.53)、B(1.2 ± 0.52)和 C(1.2 ± 0.60)中,GSDMD 与 N 的平均相对表达量高于 KN,但不显著。GSDMD 与 Beta Actin 的相对表达,A 和 B 同样高于 C、KN 和 N:给予巨蛇头鱼精氨酸的脑外伤模型大鼠的TLR-4、TNF-α、Caspase-3的表达和脑组织损伤的组织病理学均低于未给予精氨酸的大鼠。同时,给予巨蛇头鱼精蛋白后,脑外伤模型大鼠 GSDMD 的表达略高于未给予精氨酸的大鼠。
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