Didanosine (ddl) and stavudine (d4T): Absence of peripheral neurotoxicity in rabbits

Warner, W.; Bregman, Carla L.; Comereski, C. R.; Arezzo, Joseph C.; Davidson, Thomas J.; Knupp, Catherine A.; Kaul, Sanjeev; Durham, Stephen K.; Wasserman, Arthur J.; Frantz, Jerry D.

doi:10.1016/0278-6915(95)00078-x

Cited by 13 publications

(7 citation statements)

References 9 publications

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“…Although a model of DDC neurotoxicity in New Zealand white (NZW) rabbits has been reported, this neuropathy was described as being predominantly demyelinating with prominent involvement of motor fibers, in contrast to the sensory axonal pathology seen in HIV-infected individuals (Feldman et al, 1992;Anderson et al, 1994). Furthermore, another group failed to reproduce this neuropathy in NZW rabbits despite using high doses of DDI and d4T for 24 weeks (Warner et al, 1995). We have been unable to establish a rodent model of DDX-induced neuropathy.…”

Section: Discussionmentioning

confidence: 99%

Establishment of a Rodent Model of HIV-Associated Sensory Neuropathy

Keswani¹,

Jack²,

Zhou³

et al. 2006

J. Neurosci.

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Human immunodeficiency virus (HIV)-associated sensory neuropathy (SN)is the most common neurological complication of HIV infection in the current highly active antiretroviral therapy era. The painful sensory neuropathy is associated with the use of dideoxynucleoside antiretrovirals, and its development limits the choice of antiretroviral drugs in affected patients. There are presently no effective therapies for HIV-SN, and moreover there has been no robust animal model of HIV-SN in which candidate therapeutic agents can be tested. In this paper, we show that we have established a rodent model of HIV-SN by oral administration of a dideoxynucleoside drug, didanosine, to transgenic mice expressing the HIV coat protein gp120 under a GFAP promoter. The neuropathy in these rodents is characterized by distal degeneration of unmyelinated sensory axons, similar to the "dying back" pattern of C-fiber loss seen in patients with HIV-SN. This model will be useful in examining mechanisms of distal axonal degeneration and testing potential neuroprotective compounds that may prevent development of the sensory neuropathy.

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Section: Discussionmentioning

confidence: 99%

Establishment of a Rodent Model of HIV-Associated Sensory Neuropathy

Keswani¹,

Jack²,

Zhou³

et al. 2006

J. Neurosci.

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“…20 However, although d4T exhibited neurotoxicity in the same study, there was no correlation with mitochondrial DNA depletion. A study in rabbits showed mitochondrial alterations in peripheral nerves after ddC treatment, 83 but similar studies with ddI and d4T showed no neurotoxic eVect in the same species, 84 although ddI has been shown to cause neurotoxicity in rats given very high doses. The well described neuropathies associated with inherited mitochondrial diseases 85 and the evidence discussed above do suggest a role for mitochondrial dysfunction in the pathogenesis of drug related neuropathy but inconsistencies do exist.…”

Section: Cardiomyopathymentioning

confidence: 98%

Mitochondrial toxicity and HIV therapy

White

2001

Sexually Transmitted Infections

185

126

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“…ddC also had an effect on structure and function of Schwann cell mitochondria [55]. In 1995 a study showed that although peripheral neuropathy has been reported in rabbits with ddC, based on clinical observations, electrophysiological measurements, and light and electron microscopy, no evidence of peripheral neurotoxicity was observed in rabbits given either ddl of d4T [56]. Rabbits as animal models of HIV peripheral neuropathy have not been used since the 1990s.…”

Section: Rabbit Model Of Atnmentioning

confidence: 99%

Animal Models of HIV Peripheral Neuropathy

Burdo

Miller

2014

Future Virol.

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The use of animal models in the study of HIV and AIDS has advanced our understanding of the underlying pathophysiologic mechanisms of infection. Of the multitude of HIV disease manifestations, peripheral neuropathy remains one of the most common long-term side effects. Several of the most important causes of peripheral neuropathy in AIDS patients include direct association with HIV infection with or without antiretroviral medication and infection with opportunistic agents. Because the pathogeneses of these diseases are difficult to study in human patients, animal models have allowed for significant advancement in the understanding of the role of viral infection and the immune system in disease genesis. This review focuses on rodent, rabbit, feline and rhesus models used to study HIV-associated peripheral neuropathies, focusing specifically on sensory neuropathy and antiretroviral-associated neuropathies.

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Didanosine (ddl) and stavudine (d4T): Absence of peripheral neurotoxicity in rabbits

Cited by 13 publications

References 9 publications

Establishment of a Rodent Model of HIV-Associated Sensory Neuropathy

Establishment of a Rodent Model of HIV-Associated Sensory Neuropathy

Mitochondrial toxicity and HIV therapy

Animal Models of HIV Peripheral Neuropathy

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