Adverse treatment reactions due to antineoplastic agents are a common form of iatrogenic injury [
1], which prevails mostly in an idiosyncratic and indiscriminate manner. Pulmonary toxicity initiated by antineoplastic drugs is becoming a more frequently documented entity. Continuous exploitation of combined modality therapies increased the prevalence of secondary lung tumors and its multiplicity [
2]. The pathological situation is usually nonspecific but some histological evidences help define the underlying agent [
3]. Several pharmacological mediators employed in the cure of
cancer have been associated with pulmonary toxicity. Mechanisms of impairment by these drugs consist of either direct pulmonary toxicity or indirect action via boosting inflammatory reactions. Risk factors for expansion of pulmonary impairments have been elucidated for a few agents but remain unclear for others. Chronic
pneumonitis/fibrosis is the most common clinical feature for most of the categories of cytotoxic drugs [
4].
Cisplatin (cis-dichlorodiammineplatinum (II) CP) is a synthetic anticancer drug generally used for the treatment of several human malignancies [
1‐
3]. Whilst, therapeutic use of CP encouraged oxidative trauma and DNA damage in various non-cancerous tissues as well e.g. kidney, liver, testis, brain, lungs etc. [
5]. CP and its different analogs are identified to mutilate DNA by making covalent adducts. This interface is seemingly liable for the organ damage including the lungs. Investigations in various rodent models verified the mutagenic and tumorigenic effects of CP. A single drug exposure produced skin and lung tumors in mice and rats, respectively [
6]. CP is an effective therapeutic for lung cancer whilst free platinum intercalates or intracalates in DNA, induces severe injuriousness in experimental animals [
2]. Cisplatin chemotherapy induced interstitial inflammation, fibrosis and structural lung damage associated with oblitrative bronchitis and increase perioperative complications in patients [
7]. Pratibah and colleagues reported that CP administration for 18 weeks outcomes in pulmonary adenomas in A/J mice, although the mechanism behind this tumor promotion is not well understood. CP mediated pathogenesis of lung might be attributed to the reduced antioxidant defense, increase lipid peroxidation and ROS production [
8]. The role of ROS in pulmonary impairment is further reinforced by the increased activity of free radical quenching enzymes in lungs confronted by a variety of toxins [
9]. Despite various endeavors, the adverse effects associated with CP remains a key reason that confines its usage and potency in cancer therapy.
Treatment with antioxidants ameliorates or reduces the advancement of lung ailments i.e., in patients with COPD, lung cancer, asthma and acute respiratory distress syndrome (ARDS). Moreover, diet containing fruits and vegetables rich in flavonoids and other antioxidant compounds could be responsible for prevention of cancer and persuasive in ameliorating chemotherapeutic drugs prompted toxicity [
10‐
12]. Adjuvant therapies that enhance the anti-tumor effects of cisplatin are actively being pursued. Globally the inquisitiveness for alternative and complementary medicines has gained much attention because of the chemo-preventive and therapeutic significance of medicinal plants in controlling of several oxidative stress-induced disorders [
13‐
15]. Innumerable plant-derived metabolites like genistein, curcumin, resveratrol, indole-3-carbinol, epigallocatechin gallate (EGCG), and proanthocyanidin are capable to enhance efficacy and reduce harmful effects of traditional chemotherapeutic agents [
16]. It is of essential requirements that therapeutic plants should be explored for their medicinal attributes; for the reason that most of the people in undeveloped countries’ practices alternative and complimentary medicines [
17‐
19]. Genus
Acacia possess species with diverse pharmacological properties, has come under extensive investigations in light of their anti-inflammatory, antitumor [
20], antioxidant [
21], wound healing [
22], chemopreventive and antimutagenic [
23] actions in various animal models [
24].
Acacia hydaspica R. Parker synonym
A. eburnea [
25] belongs to family leguminosae is therapeutically important plant. The plant is normally used as fodder [
25,
26] and is locally employed as antiseptic. In our previous lab experiments we revealed antioxidant, anti-cancer, anti-hemolytic, anti-inflammatory, antidepressant, and anxiolytic proficiencies of
A. hydaspica [
27‐
30]. Various bioactive metabolites were detected in
A. hydaspica i.e., 1,2-Benzenedicarboxylic acid mono (2-ethylhexyl) ester, α-Amyrin, 2,6-dimethyl-N-(2-methyl-à-phenylbenzyl) aniline, Vitamin E, and Squalene, gallic acid, rutin, catechin, caffeic acid. Ethyl acetate fraction (AHE) of
A. hydaspica showed excellent antioxidant activity in vitro. 7-
O-galloyl catechin, +catechin and methyl gallate are the main bioactive metabolites with anticancer potential against breast and prostate cancer [
27‐
29]. Various species of genus
Acacia were reported for their antioxidant and protective potentials against lung toxicity in animal models [
31].
A. hydaspica AHE fraction showed significant hepato-protective potential against cisplatin persuaded hepatic damage in rats [
32]. Shahid and colleagues reported the protective potential of methanolic extract of
Acacia catechu Willd bark. (MEBA) against the lung toxicity induced by B(a)P in mice. Pretreatment with MEBA at two different doses (200 and 400 mg/kg body weight) significantly ameliorates B(a)P-induced increased toxicity markers and activities of detoxifying enzymes along with the levels of glutathione content. It also significantly attenuated expression of apoptotic and inflammatory markers in the lungs and attenuated destruction of alveolar architecture and necrosis of the alveolar epithelium of the lungs [
33].
Acacia honey ameliorated sodium arsenide persuaded oxidative trauma in the cardiac, pulmonary, and renal tissues of rats due to its antioxidant potential and polyphenol components [
34]. Nikbakht et al. indicated that Gallic acid protect lungs from bleomycin induced increased in inflammatory or fibrotic changes, collagen content, levels of malondialdehyde (MDA), and pro-inflammatory cytokines such as TNF-α and IL1β. Furthermore Gallic acid reverse histological alterations and significantly increased non-enzymatic (total thiol) and enzymatic (glutathione peroxidase (GPx) antioxidant contents in the bleomycin treated rats’ lung tissue by its antioxidant properties [
35]. Gallic acid inhibit oxidative damaged to DNA in lymphocytes, liver, colon and lungs of rats [
36]. The development of secondary malignancy as a result of CP chemotherapy can be also prevented with polyphenol treatment as indicated by the study of Mimoto et al. illustrating that Epigallocatechin Gallate (ECGC) inhibit CP prompted pulmonary tumorigenesis and weight diminution in A/J mice [
2,
37].