Sperm head abnormality and mutagenic effects of aspirin, paracetamol and caffeine containing analgesics in rats
U Ekaluo, E Ikpeme, A Udokpoh
analgesics, aspirin, caffeine, mutagenicity, paracetamol, sperm head abnormality
U Ekaluo, E Ikpeme, A Udokpoh. Sperm head abnormality and mutagenic effects of aspirin, paracetamol and caffeine containing analgesics in rats. The Internet Journal of Toxicology. 2008 Volume 7 Number 1.
The mutagenic effects of analgesics with aspirin, paracetamol and caffeine combinations were evaluated in a male rat model using a short-term in vivo
had a synergistic effect that significantly increased both the frequency of abnormal sperm heads to 13.5% and the mutation index to 8.00. Sperm head abnormality was also proportional to mutation index
Analgesics with aspirin, paracetamol and caffeine combinations are ingested for many reasons including: general pains, headaches, fevers, cold, flu, rheumatoid arthritis, circulation problems (1) and in cases of dependent-addiction (2).
In recent years, there has been an increasing awareness and realization of the genotoxic potentials of a wide variety of drugs, food additives, environmental pollutants (3, 4) and other socially acceptable compounds such as aspirin and caffeine (5). Habitual ingestion of aspirin and caffeine has been shown to be capable of inducing structural chromosomal aberrations in somatic cells
Aspirin is one of the most widely used analgesics available without prescription in several parts of the world (7). Mutagenic studies of aspirin in mammals are not common and are mostly limited to
There are conflicting reports on potentials of paracetamol as an experimental carcinogenic agent, although evidences implicate metabolites of paracetamol and phenacetin as being active experimental carcinogenic agents (2, 10, 11). Paracetamol has also been reported to inhibit DNA synthesis by 70-90% at 1hour following an oral dose in the spleen, testis, thymus, stomach, small intestine and bone marrow (12).
Caffeine is often used with aspirin and paracetamol to augment their antipyretic and analgesic effects (13). There is a strong relationship between the ingestion of various combinations of analgesics with caffeine resulting in approximately 2-fold increase in the risk of cancers of the pelvic, kidney, bladder and urinary tract (2, 11).
In view of such findings, this study set out to further explore the effect of caffeine on the mutagenicity of analgesics with aspirin, paracetamol and caffeine combinations in rats as model using short-term
Materials and methods
Forty-eight healthy isogenic strains of male albino rats (
The following analgesics were obtained from reputable pharmacies:
The rats were sacrificed after 90 days of treatment, and the sperm suspension was obtained by mincing the epididymes with fine scissors into 1mg aliquots in physiological saline. The sperm suspensions were mixed with 1% eosin Y solution (10:1) for 30 minutes and air-dried smears were prepared on glass slides for the sperm head abnormality test. The slides were examined for percentage abnormalities in every 200 spermatozoa observed on each slide and five air-dried smears were prepared on glass slides for each sample. Frequency of abnormal sperm heads was calculated according to Ekaluo (14). Mutation factor and mutation indices were also calculated as shown below. Differences between the means of the control and experimental groups were compared using the analysis of variance (ANOVA) test.
General observations showed that all the rats in the study looked healthy and there was a general increase in body weights of all rats in both treatment and control groups during the treatment period. The increases in body weights of the rats indicated that the five analgesics had no adverse effect on growth and body weight of the rats.
A 90-day exposure to recommended doses of the five analgesics,
The presence of caffeine in
Figure 1 shows the relationship between frequency of abnormal sperm heads and mutation index. The frequency of abnormal sperm heads recorded for rats treated with five analgesics with aspirin, paracetamol and caffeine combinations (
Discussion and Conclusion
In the study, a significantly increased frequency of sperm head abnormalities was observed in the spermatozoa of treated rats. Increases in the incidence of abnormal sperm have been reported after treatment of male albino rats with formaldehyde (15) and analgesics (5). It has been reported that high temperatures, extreme nutritional deficiencies and some diseases can cause sperm abnormalities in a wide range of species including mice and man (16). Male Wister rats fed on a diet containing 36% of total calories as ethanol for 41 days caused similar sperm abnormalities as those reported in other mammalian species, and the mean frequency in control groups was 1.2%, with the range of 1.0-1.6% (17). The frequency of the control group here is also within this range. Various anti-inflammatory analgesics and certain steroids inhibit the production of prostaglandins (18), and inhibition of prostaglandins is known to interfere with spermatogenesis.
Although, the precise mechanism by which aspirin, paracetamol and caffeine containing analgesics cause sperm head abnormalities has not been fully established, generally, damage to the sperm cell by substances may occur by one of three mechanisms: physiological, cytotoxic and genetic. The morphological abnormalities might have been caused by alterations (deletions, point mutation or a combination of both) in testicular DNA that in turn disrupts the process of differentiation of spermatozoa (12, 19), exposure to chemicals that could produce pituitary-hypothalamic or sex hormonal effects which in turn could affect spermatogenesis (18, 20, 21) and exposure of the seminal fluid to chemicals, resulting in functional or structural impairment of sperm cells (20, 21).
The tested analgesics showed significant effects in an increasing order of
The work has provided some data and information that may be useful for public health. There is the need for regular public health checks on the consumption of some socially acceptable compounds such as analgesics with aspirin, paracetamol and caffeine combinations, since the presence of caffeine in