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. 2014 Jan 9;11(1):919-33.
doi: 10.3390/ijerph110100919.

Toxicity of gutkha, a smokeless tobacco product gone global: is there more to the toxicity than nicotine?

Daniel N Willis  1 , Mary A Popovech  2 , Francesca Gany  3 , Carol Hoffman  4 , Jason L Blum  5 , Judith T Zelikoff  6
Affiliations

Toxicity of gutkha, a smokeless tobacco product gone global: is there more to the toxicity than nicotine?

Daniel N Willis et al. Int J Environ Res Public Health. .

Abstract

The popularity of smokeless tobacco (ST) is growing rapidly and its prevalence of use is rising globally. Consumption of Gutkha, an addictive form of ST, is particularly common amongst South Asian communities throughout the World. This includes within the US, following large-scale immigration into the country. However, there exists a lack of knowledge concerning these alternative tobacco products. To this end, a study was carried out to determine the toxicity of gutkha, and what role, if any, nicotine contributes to the effects. Adult male mice were treated daily for 3-week (5 day/week, once/day), via the oral mucosa, with equal volumes (50 μL) of either sterile water (control), a solution of nicotine dissolved in water (0.24 mg of nicotine), or a solution of lyophilized guthka dissolved in water (21 mg lyophilized gutkha). Serum cotinine, measured weekly, was 36 and 48 ng/mL in gutkha- and nicotine-treated mice, respectively. Results demonstrated that exposure to nicotine and gutkha reduced heart weight, while exposure to gutkha, but not nicotine, decreased liver weight, body weight, and serum testosterone levels (compared to controls). These findings suggest that short-term guhtka use adversely impacts growth and circulating testosterone levels, and that gutkha toxicity may be driven by components other than nicotine. As use of guthka increases worldwide, future studies are needed to further delineate toxicological implications such that appropriate policy decisions can be made.

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Figures

Figure 1
Figure 1
Experimental approach used to assess the toxicity of gutkha and nicotine in a mouse model.
Figure 2
Figure 2
Mice treated for 3 week with either nicotine or gutkha had elevated serum cotinine levels. Cotinine levels in water-treated control mice were below assay detection limits at all time points evaluated. Data represented as means +/− standard deviation, n = 3 mice/group for each time point.
Figure 3
Figure 3
Overall body weight change after exposure for 3 week to either water, nicotine or gutkha. Body weight decreased in gutkha-exposed mice compared to controls (p < 0.05), but not in mice exposed to nicotine alone. n = 7–12 animals/group.
Figure 4
Figure 4
Relative (a) and absolute (b) heart weight. Both relative heart weight (organ weight/BW) and absolute heart weight was significantly decreased in both nicotine- and gutkha-exposed mice compared to controls (p < 0.05). Data represented as means +/− standard deviation, n = 7–12 mice/group.
Figure 5
Figure 5
Relative (a) and absolute (b) liver weight. Relative (organ weight/BW) was significantly decreased in gutkha-exposed mice (p < 0.05), but not in mice exposed to nicotine alone (compared to controls). Absolute heart weight was decreased in both nicotine- and gutkha-exposed mice compared to controls (p < 0.05). Data represented as means +/− standard deviation, n = 7–12 mice/group.
Figure 6
Figure 6
Serum testosterone levels were significantly decreased in gutkha-exposed mice (p < 0.05), but not in mice exposed to nicotine alone compared to controls. Data represented as means +/− standard deviation, n = 7 mice/group.
Figure 7
Figure 7
Relative fold-change in gene expression of CYP2A5 in the liver was significantly increased in gutkha-treated mice (p < 0.05), but not in mice exposed to nicotine alone compared to controls. Data are represented as means +/− standard deviation, n = 7 mice/group.
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