Ganglioside treatment of alcoholic neuropathies: Experimental and clinical aspects

A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important comorbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC) (50 mg/kg) neuropathy was mitochondrial dependent and PKCε independent, and alcohol-induced painful neuropathy, PKCε dependent and mitochondrial independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for one week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial dependent but PKCε independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction.

show abstract

“…, 1978, 1983; Bosch et al. , 1979; Scott & Edwards, 1980; Oakes & Pozos, 1982; Massarotti, 1983; Riopelle et al. , 1984; Scott et al.…”

Section: Discussionmentioning

confidence: 99%

Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms

Ferrari

Levine

2010

Eur J of Neuroscience

View full text Add to dashboard Cite

show abstract

“…Hence our primary objective for preparing the antibody was to determine whether the intensive immunization of rabbits with highly purified gangliosides would induce any neurological symptoms since several reports have implicated the development of neurological disorders in animals by direct immunization with GM1 (7,8). These reports raise doubts as to the potential benefits of using gangliosides as a therapeutic agent for the treatment of a variety of neurological disorders (9)(10)(11)(12)(13). Here, we show that despite the high titer anti-gangliside antibodies in immunized rabbits for a period of 6 months, no obvious neurological and neuropathological changes in the experimental animals were observed.…”

Section: Introductionmentioning

confidence: 99%

Lack of Apparent Neurological Abnormalities in Rabbits Sensitized by Gangliosides

Dasgupta

2004

Neurochem Res

View full text Add to dashboard Cite

Two very high titer polyclonal antibodies against two ganglioside antigens, GM1 and GD1a, have been raised in New Zealand white rabbits using a homogeneous suspension of the highly purified antigens in Keyhole Limpet Hemocyanin and Freund's adjuvant. The antisera were prepared over a period of 6 months with repeated injections of the ganglioside suspension, followed by an intravenous injection of the purified ganglioside solution, and collecting the serum (approximately 50 ml) at defined time intervals. The GM1-antibody, thus prepared, showed a cross reactivity toward GDlb and asialo-GM1 (GA1), while the GDla-antibody reacted with GD1a, GM1 and GA1 and GD1b as determined by immuno-overlay and ELISA methods. The titer for GM1 antiserum, determined by'ELISA, was greater than 1/10,000 dilution while the titer for GD1a antibody was greater than 1/5000 dilution. No neurological or behavioral abnormality was observed during the period of antiserum production. To evaluate any likely pathological damage caused by such a high titer ganglioside-antibody, autopsy of CNS as well PNS tissues from the rabbits were carried out after the final bleeding. No obvious pathological changes, including demyelination, were noted in any of the four rabbits. These observations cast doubt as to the direct effect of anti-ganglioside antibody induced neurological and pathological disorders.

show abstract

“…Vitamin substitution is helpful in cases where real deficiency exists, and this seems to be rather uncommon in western countries. Interesting efforts on ganglioside treatment of alcoholic polyneurophaties have recently been performed but this aspect requires further studies (39,40). Along with symptomatic therapy sometimes necessary for the patients, the only effective treatment of alcoholic polyneuropathy seems to be abstinence.…”

Section: Prognosis and Treatment Of Alcoholic Polyneuropathymentioning

confidence: 99%

Alcoholic Polyneuropathy

Juntunen

1985

Journal of Internal Medicine

View full text Add to dashboard Cite

Ganglioside treatment of alcoholic neuropathies: Experimental and clinical aspects

Cited by 13 publications

References 8 publications

Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms

Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms

Lack of Apparent Neurological Abnormalities in Rabbits Sensitized by Gangliosides

Alcoholic Polyneuropathy

Contact Info

Product

Resources

About