Atrophy and Inflammatory Changes in Salivary Glands Induced by Oxidative Stress after Exposure to Drugs and Other Chemical Substances: A Systematic Review

Abstract

Background and Objectives: Oxidative stress is involved in the alterations at the level of salivary glands, being the cause of oral pathologies like xerostomia, periodontitis, gingivitis, leucoplakia, and cancer. It is known that antioxidants can reverse changes induced by drugs or other chemicals in some organs, but the question is whether these substances can reduce or revert the effects of oxidative stress at the salivary gland level. Our aim was to find histopathological data at the level of salivary glands supporting the hypothesis of the reversal of oxidative stress-induced changes after the treatment with substances with antioxidant effect. Materials and Methods: A systematic search was conducted in PubMed, Science Direct, and Springer databases, including research articles on oxidative stress histological aspects and oxidative stress biomarkers induced by drugs or other chemicals on salivary glands. Results: Out of 1756 articles, 25 articles were selected with data on tissue homogenate used for biochemical analysis of oxidative and antioxidative markers, along with routine hematoxylin eosin (HE) and immunohistochemical analysis used for histopathological and immunohistochemical diagnosis. Drugs (antineoplastic drugs, antibiotics, and analgesics), alcohol, heavy metals, and fluoride can cause oxidative stress, resulting in morphological changes in different tissues, including in salivary glands. There are many antioxidants but only a few were evaluated regarding the effects on salivary glands in animal studies, such as hesperidin and selenium, which can reverse the damage induced by cyclophosphamide; 10-dehydrogingerdione (10-DHGD), a compound extracted from ginger, which has a protective effect against the oxidative stress and apoptosis induced by tramadol; and glycyrrhizic acid, which may repair the injuries incurred after the administration of sodium nitrite. Conclusions: Substances such as hesperidin, selenium, 10-dehydrogingerdione, and glycyrrhizic acid are antioxidants with proven restorative effects on salivary glands for the damage induced by oxidative stress after exposure to drugs and other chemical substances; however, demonstrating their similar effects in human salivary glands is challenging.

Avaliação da Hipossalivação e Xerostomia em Pacientes Oncológicos em Tratamento Quimioterápico

“…Medicações quimioterápicas podem levar a alterações salivares. Estudos primários sumarizados em uma revisão sistemática 21 investigaram os efeitos bioquímicos e histológicos de fármacos antitumorais nas glândulas salivares. Os medicamentos anticâncer podem induzir a morte celular por meio do estresse oxidativo, desencadeando a formação de espécies reativas de oxigênio e resultando em apoptose das células produtoras de saliva.…”

“…A ciclofosfamida, por exemplo, utilizada no tratamento do câncer e como imunossupressor, afeta as glândulas salivares, causando xerostomia por causa da redução na produção de saliva, com efeitos persistentes. Já o 5-fluorouracil, utilizado em tumores sólidos, também induz atrofia das glândulas salivares e xerostomia, associado ao estresse oxidativo 21 .…”

Gemigliptin Improves Salivary Gland Dysfunction in D-Galactose-Injected Aging Rats

“…In contrast, amylase levels decreased in the salivary glands of aging rats. Oxidative stress, caused by the accumulation of ROS, altered secretion functions, such as saliva secretion, salivary amylase, and calcium levels, in the salivary glands of rodents [ 46 ]. Consequently, the administration of gemigliptin in aging rats resulted in an increase in saliva flow and amylase levels in saliva, while levels of amylase in the salivary glands decreased.…”

Reversal of Valproate‐Induced Major Salivary Gland Changes By Moringa Oleifera Extract in Rats

“…Drugs for the treatment of various diseases can cause adverse effects such as salivary gland dysfunction, salivary gland hypofunction, sialorrhea (excessive salivation), and dry mouth. [1] Valproic acid/sodium valproate (VA), or 2-propyl pentanoic acid, is a branched short-chain fatty acid derived from valeric acid. Besides being used in the treatment of epilepsy, VA is also an effective drug for use in psychiatric disorders such as anxiety, bipolar disorder, and migraine.…”

“…The main task of the salivary glands is to produce saliva, which contains enzymes that aid digestion and protect against microbes, and to moisten the mouth. Drugs for the treatment of various diseases can cause adverse effects such as salivary gland dysfunction, salivary gland hypofunction, sialorrhea (excessive salivation), and dry mouth [1] …”