High dose gabapentin does not alter tumor growth in mice but reduces arginase activity and increases superoxide dismutase, IL-6 and MCP-1 levels in Ehrlich ascites

Abstract

ObjectivesThe purpose of this study was to evaluate the effect of gabapentin on Ehrlich tumor growth in Swiss mice, a highly aggressive and inflammatory tumor model. Mice were grouped into sets of 5 animals and treated from days 2 to 8 with gabapentin 30 mg/kg body weight (G30) or 100 mg/kg body weight (G100), or normal sterile saline (control).ResultsThe mice were euthanized on day 10. Tumor growth, tumoricidal agents and inflammatory cytokines levels were assessed. At day 10, G30 and G100 mice gained weight, but there were no differences in tumor cell count or in ascites volume. In G100, there was a reduction in arginase and an increase in SOD activities. There was an increase in IL-6 and MCP-1 levels, especially in G100, but no alterations in TNF-α. There was no direct evidence of tumor induction by gabapentin. However, the findings suggest that its use modulates immune response to a more effector and less deleterious profile, with increase in activity of anti-oxidant enzymes and in cytokines that favor activation of macrophages, which could improve the general status of the tumor host.Electronic supplementary materialThe online version of this article (10.1186/s13104-019-4103-9) contains supplementary material, which is available to authorized users.

Second Generation of Antiepileptic Drugs and Oxidative Stress

“…GBP effectively prevents oxidative stress in various animal models [ 41 , 48 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 61 ]. Oxidative stress is associated with gliosis and neuronal damage that leads to apoptosis [ 90 ].…”

“…Hence, restoring mitochondrial homeostasis seems to be an encouraging strategy in protecting against seizure-induced oxidative stress [ 91 ]. It should be emphasized that, in most studies confirming the antioxidative activity of GBP, this drug was administered in doses up to 100 mg/kg [ 41 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 61 ].…”

“…However, it seems that the influence of GABA-ergic transmission on the production of ROS and RNS depends on the dose of the used drugs and the pathological conditions in the tissue. In the case of oxidative stress, the introduction of a drug elevating GABA concentration causes a decrease in the oxidation markers and neuroprotection [ 24 , 34 , 35 , 41 , 48 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 61 ]. This is evidenced by the antioxidant activity of muscimol, a GABA-A receptor agonist, and diazepam, a GABA-A positive allosteric modulator, in a mouse with immobilization stress and in PTZ-induced seizure activity, respectively [ 60 , 63 ].…”

“…GBP and TGB are recommended as first-line co-analgesic drugs in the treatment of cancer pain, effectively reducing suffering and providing improvement in sleep and quality of life, and also allowing a reduction in opioid doses [ 60 ]. Whether GBP could affect tumor progress was investigated by assessing the effect of GBP administration on Ehrlich tumor growth in Swiss mice [ 61 ]. A decrease in SOD activity and impaired free radical removal promotes tumor progress [ 62 ].…”

“…However, GBP therapy increased the weight of the mice compared to the control, and importantly, this was not caused by ascites or tumor progress. The authors are of the opinion that despite GBP therapy not affecting tumor development, the effects of GBP at the molecular level, such as increased SOD activity, IL-6 and MCP-1 levels and reduced arginase activity, may have a positive effect on the patients’ general condition [ 61 ].…”