EFFECT OF LOW LEVEL HELIUM-NEON LASER ON ISONIAZID-INDUCED HYPERGLYCEMIA IN MICE

G.R. Sadeghipour, R. Yousefi, S. Hejeri, A.R. Abassian, M.R. Zarrindast PhD

Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

  • Abstract

    Background and Objective-Different properties of low-level He-Ne laser has been under investigation, one of which is its effect on blood sugar level. In the present study, the effect of low-power laser on hyperglycemia induced by isoniazid has been investigated in mice.
    Methods-One hundred male albino mice were divided into four groups: group 1 received intraperitoneal isoniazid, group 2 was treated with laser after isoniazid administration, group 3 was given saline and then irradiated by laser, group 4 received only saline. Laser irradiation was performed at 5 epigastric areas, 45 seconds each. This procedure was repeated twice daily for 9 days in groups 2 and 3.
    Results- The data indicated that intraperitoneal (IP) injection of isoniazid (100mg/kg) produces hyperglycemia in comparison to group 4. When isoniazid administration coincides with laser irradiation, the blood sugar level will not change significantly compared to the control group.
    Conclusion-It could be concluded that He-Ne laser is capable of reversing the isoniazid-induced hyperglycemic effect on mice liver, and might have a protective property in case of drug-induced hyperglycemia.

    •

    Keywords · Helium-Neon laser · isoniazid · hyperglycemia

    Introduction

    Previously promotive and stimulative effects of low-level laser have been described.1-3 It has been shown that low intensity laser irradiation promotes wound healing 3,4-6 and increases neurotransmitter release.7 It may also increase the neuronal outgrowth.8 Laser irradiation to liver mitochondria leads to the development of a new subpopulation of these structures9, thereby increasing ATP level.10 The H+/e- ratio of the cytochrome-C oxidease in the mitochondrial products shows an increase11,12 and this in turn stimulates transcription and translation activities13 and cell proliferation.1,2,14

    There are many articles reporting the effects of low power lasers on the liver.9,11,15,16 The effects of low power laser on tissues can be divided into direct and systemic effects.17

    Isoniazid is a drug used for the treatment of tuberculosis. In high doses, it can cause hepatotoxic and neurotoxic effects.18-21 Isoniazid-induced hepatotoxicity manifests as either cell necrosis, steatosis or a combination of both.19,20,22 Steatosis is due to a rise in serum free fatty acids level, increased uptake of free fatty acids by the liver, increased hepatic triglyceride biosynthesis, and decreased lipoprotein secretion.22 Hyper-glycemia is also one of the side effects of isoniazid administration.21 In the present study, the effect of low power laser on isoniazid-induced hyper-glycemia has been studied.

    Materials and Methods

    One-hundred male albino mice (25-30 g) were used in these experiments. They were housed 25 per cage, in colony rooms with 12/12 h light/dark cycle at 22±2 ° C. The animals had free access to food and tap water except during the time of experiments. Isoniazid was obtained from Darupakhsh Co (Tehran, Iran).

    Laser irradiation was delivered by a low power helium-neon laser (Atomic Energy Organization, Tehran, Iran). The parameters were: wavelengh, 632.8 nm, continuous wave, power output 10 mW, energy density 5 Joule/cm2 (J/cm2) exposure time for each point 45 sec. During laser administration the animals were restrained in the experimenter’s hand while laser beam was applied to 5 points of shaved epigastric surface on mice’s abdomen.

    Plasma glucose concentrations were measured by a glucose oxidase method using a Beckman Glucose Analyzer II (Beckman Fullerton, CA) and Diagnosticom kit.

    Results were presented as means and standard errors and statistical significance were determined by non-paired student’s t-test.

    The animals were divided into four groups. Group 1 received isoniazid (100 mg/kg) intraperitoneally (IP) twice daily (6 h intervals) for a period of 9 days. Group 2 received isoniazid 45 minutes prior to laser irradiation 2 times a day for a period of nine days (as group 1). Group 3 received laser plus saline (10 ml/kg) injection. Group 4 (control group) received saline (10 mg/kg) and were handled as other groups. Blood samples were collected 24 h after the last drug administration and the animals were deprived of food during that time.

    Results

    The blood sugar level in the control group, as shown in the Figure 1, was 55±6.6 mg/dl. This level was almost doubled when the mice received intraperitoneal isoniazid injections (104±6.2 mg/dl, P<0.001). This hyperglycemic effect was neutralized in group 2, in which the mice received both laser irradiation and isoniazid injections. The blood sugar level in this group did not rise as the isoniazid group and remained in a normal level (49.5±4.8 mg/dl). This level was significantly lower than the observed level in group 1 (isoniazid only) (P<0.001).

    Discussion

    Isoniazid has been shown to induce hepatotoxicity. One of the major reasons for hepatotoxicity is lipolysis (release of free fatty acids and cholesterol into the blood stream). To compensate the hyperlipidemia by the drug, lipid acids and triglycerides may be taken up by the liver and in turn lead to steatosis.19,20,22 In the present study, isoniazid-induced hyperglycemia may be due to the drug-induced hepatotoxic disorder.

    There is evidence that the energy dose of 5 J/cm2 reduces the intensity of the protein and fat degeneration, parenchymal necrosis and inflammatory infiltration and prevent toxic hepatitis.16 There is also evidence that the dose of 5 J/cm2 has a proliferative effect on hepatocytes9,11 , and affects the metabolic activities of liver cells.15

    Our study shows that isoniazid-induced hyperglycemia can be reversed by low-power laser irradiation. Whether this response is due to influence on hepatotoxicity and/or other factors, should be further investigated. It can be postulated that laser irradiation compensates the hepatotoxic effect induced by isoniazid.

    Acknowledgment

    This work was funded by "Laser in Medicine Research Group", Student Scientific Research Center of Tehran University of Medical Sciences. The authors thank Dr. Shabnam. Ozlati for her supports.

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