Inhibition of rat parotid gland growth response induced by chronic isoproterenol following treatment with quinolone antibiotics

Abstract

While antibiotics are broadly used in dental and medical therapy, little attention has been directed towards the potential toxic side effects of antibiotics on tissue regeneration. Here we examined the effect of a quinolone antibiotic, pefloxacin (Rhone Poulenc) on rat parotid gland responses to chronic isoproterenol treatment. Groups of rats received injections of isoproterenol to induce glandular growth, saline (controls), pefloxacin, or isoproterenol and pefloxacin in combination. Parotid gland weight decreased significantly after pefloxacin treatment for 7 days as well as inhibiting glandular enlargement provoked by isoproterenol. The same trend was observed for the rates of DNA synthesis, with the incorporation of [3H]-thymidine in isoproterenol/pefloxacin-treated rats reduced to 49% of isoproterenol treatment alone levels. Saline-treated animals were 42% of the rate of [3H]-thymidine incorporation into DNA observed in isoproterenol treated rats. While isoproterenol treatment increased steady-state mRNA levels for fos, jun, myc, src, c-erbB-2, ras and topo II, inclusion of pefloxacin with the isoproterenol regimen blocked these increases. Pefloxacin treatment by itself did not alter proto-oncogene mRNA levels in the parotid gland. Glandular amylase activity was decreased in the pefloxacin treated group, while the combination of isoproterenol with pefloxacin did not decrease glandular amylase levels to the extent of that observed with beta-agonist treatment alone. In acute experiments, pefloxacin significantly decreased the volume of saliva secreted by the parotid gland. These results suggest that quinolone-based antibiotics disturb the secretory function of the parotid gland and can inhibit cell proliferation and regeneration.

Modification of Innervation Pattern by Fluoroquinolone Treatment in the Rat Salivary Glands

“…The wet weight of each salivary gland decreased significantly related to the control animals similar to our previous results (Kelentey et al, 1996). Histological examination of sections from PEF-treated 2.…”

“…This result may indicate that besides the previously suggested non-neuronal mechanisms (Baum, 1987;Edgar, 1992;Kelentey et al, 1996), the neurotoxic effect of FQAs also contribute to the impaired saliva secretion. Our present finding is in accordance with recent experimental data showing that chemical denervation of salivary glands by botulinum toxin caused temporary atrophy of acini, and it was accompanied by reduced expression of amylase (Teymoortash et al, 2007).…”

“…Therefore, it seems very likely, that the decrease in the number of SP and CGRP-IR fibers following PEF treatment may indicate the alteration of both the autonomic and sensory innervation of salivary glands. In our previous experiment (Kelentey et al, 1996), we have studied the effect of PEF treatment on the pilocarpine-stimulated saliva flow of parotid glad. The pilocarpine administration, a muscarin receptor agonist parasympathomimetic drug, resulted in a 57% reduction in the saliva flow, and a 35% decrease was measured in the amylase activity of parotid gland.…”

“…The underlying mechanism of impaired function of salivary glands caused by FQA was studied in our earlier experiments. The pefloxacin (PEF) treatment, one of the FQA antibiotics, resulted in a significant weight loss of parotid gland and it was accompanied by the reduced saliva volume and decreased amylase activity (Kelentey et al, 1996). The molecular mechanism of decreased amylase activity caused by PEF treatment was explained by the topoisomeraze II inhibition and subsequent disorder of DNA synthesis (Kelentey et al, 1996).…”

“…The pefloxacin (PEF) treatment, one of the FQA antibiotics, resulted in a significant weight loss of parotid gland and it was accompanied by the reduced saliva volume and decreased amylase activity (Kelentey et al, 1996). The molecular mechanism of decreased amylase activity caused by PEF treatment was explained by the topoisomeraze II inhibition and subsequent disorder of DNA synthesis (Kelentey et al, 1996). Functional and structural damage of rat submandibular and parotid glands was also reported in acute experiments following application of other FQA, such as ciprofloxacin and ofloxacin (Abdollahi and Isazadeh, 2001;Abdollahi et al, 2003).…”