Toxicity, Immunosuppressive Effects and Carcinogenic Potential of Volatile Nitrites: Possible Relationship to Kaposi's Sarcoma

Abstract

Volatile nitrite in the form of amyl nitrite was used for 100 years for the treatment of angina pectoris. In spite of recognized toxicity, its use in this form was considered safe. During the 1960s prescriptions were not required for purchase of amyl nitrite (called poppers) and its use for recreational purposes became popular. With reinstatement of the prescription requirement in 1969, non-medicinal, street-variety volatile nitrites were made commercially available in the form of mixtures of impure butyl and isobutyl nitrite; some of these preparations also included amyl nitrite. These products have been found to be profoundly immunosuppressive for human lymphocytes in vitro, and their by-products when metabolized into N-nitroso compounds have been known to be highly carcinogenic in many animal species. Recreational use of inhaled volatile nitrites is prevalent among male homosexuals and the compounds have been suspected as possible cofactors in Kaposi's sarcoma associated with the Acquired Immune Deficiency Syndrome (AIDS). This association could be explained by nitrite-induced vasodilation of rectal mucosal vessels providing a port of entry for a transmissible agent, by direct immunosuppression of the host allowing expression of a potentially oncogenic virus by co-carcinogenic effects of by-products by themselves or in conjunction with other putative cofactors such as cytomegalovirus. Nitrites should continue to be considered as a possible cofactor in the etiology of Kaposi's Sarcoma among male homosexuals and possibly those with other manifestations of AIDS.

Poppers: Epidemiology and Clinical Management of Inhaled Nitrite Abuse

“…6 At that time, nitrite abuse was also believed by some to be associated with the common opportunistic infection Kaposi's sarcoma. [7][8][9] Many researchers have provided evidence to disclaim these associations, but within the popular media, nitrites may continue to be perceived as linked to these diseases.…”

Long-term nitrite inhalant exposure and cancer risk in MSM

“…Despite their potential for harmful effects at high doses [15,16,20–22], popper use remains prevalent among MSM around the world, ranging from 20–40% among MSM cohorts in the United States, Canada, United Kingdom, and China [12,14,19,23–26]. Unlike stimulants and other recreational drugs that correlate with high-risk behavior among MSM, poppers have transient immunosuppressive effects in animal models, particularly at high doses with frequent exposure [21,27–29]. Poppers gained notoriety early in the AIDS epidemic as a potential cause of AIDS and Kaposi sarcoma [16,30], but these notions were later debunked [31,32].…”

Transient visual loss after amyl Isobutyl nitrite abuse

“…1,2 This facilitates increases sexual pleasure and has aphrodisiac effects. Usually the drug, known as a "popper," is taken by inhalation and very rarely causes serious systemic side effects 3 and no retinal complications have ever been reported.…”