## 4 Discussion  
Antineoplastic drugs not only kill pathologically growing cancer cells in the body, but they also destroy rapidly proliferating normal cells. Therefore, many cancer drugs also have side effects on tissues including bone marrow, blood cells, and other rapidly proliferating cells. Although kidney cells do not divide fast, their high blood flow, ability to concentrate poisons in the medullary interstitium, and particular transporters in the tubular epithelium make them highly susceptible to toxic injury [28; 29]. Tubulopathies, acute renal failure, and glomerulopathies as prevalent clinical manifestations, and nephrotoxicity, defined as any kidney injury directly or indirectly caused by drugs, occur when kidney-specific detoxification and excretion does not work properly due to damage or destruction of  
Figure 12: LIME results for the third rat in the MTX-treated group. kidney function by exogenous or endogenous toxic substances [3]. Drugs can have harmful effects on many targets in the kidney via diverse biological processes [30]. Because active clearance, reabsorption, intracellular concentration, and the local interstitial accumulation of medicines occur largely at this region in the kidney, the proximal tubule is of special relevance for nephrotoxicity research. The proximal tubule's continuous exposure to high concentrations of drugs and their toxic metabolites, combined with the high energy demand of epithelial cells in this region, makes it especially vulnerable to noxious stimuli that can lead to tubular cell toxicity and, eventually, to kidney failure [31; 32]. Drug toxicity frequently occurs in the kidney, which is the principal control mechanism that maintains the body's homeostasis and is hence highly vulnerable to xenobiotics [33]. Understanding the harmful mechanisms of nephrotoxicity can help in the creation of medications with fewer side effects and more therapeutic advantages. Mechanisms of drug-induced nephrotoxicity include tubular cell toxicity, inflammation, changes in glomerular hemodynamics, crystal nephropathy, thrombotic microangiopathy, and rhabdomyolysis. New biomarkers that can detect kidney damage early and more precisely must be discovered and developed in order to effectively prevent drug-induced nephrotoxicity. Biomarker candidates for nephrotoxicity assessment have been identified. Although some fail to provide specificity and sensitivity, studies are promising [34; 35; 36]. The most effective technique for preventing or limiting nephrotoxicity is to have sensitive and specific biomarkers available early in the drug development process, well before clinical trials begin. In preclinical models and clinical settings, these biomarkers should be able to accurately anticipate toxicity, enabling drug developers to successfully counsel patients to modify or abandon potential medicines and switch to alternatives that affect the same target without toxicity [36]. In this study, genomic, histopathological, and immunohistochemical analyses were performed with samples taken from rats with nephrotoxicity induced by an antineoplastic drug, methotrexate, and from rats in the control group, in order to determine biomarkers for drug-induced nephrotoxicity. lncRNA sequence analyses, which are known to be involved in many regulatory mechanisms in the case of transcription and subsequent gene expression as well as fulfill primary functions for quite different biological processes, were performed from tissue samples taken within the scope of the genomic analyses. According to the histopathological analyses performed in this study, the outer leaf of the Bowman capsule in the renal corpuscle and the glomerular tuft in the cortex was normal in the kidney sections stained with the hematoxylin and eosin staining method in the control group. In the MTX-treated group, significant areas of inflammation were observed in the intertubular areas of the cortex in the preparations examined by the hematoxylin and eosin staining method.