1. Introduction
The liver is an essential organ in the body, playing a significant role in controlling a number of biological activities such as metabolism, secretion, and storage. Therefore, it protects the body from toxic substances through detoxification and the elimination of xenobiotics from the body [
1,
2]. This exposes the liver to a variety of endogenous and external harmful substances that can cause hepatotoxicity [
3].
Many regularly used chemicals and drugs cause cellular and metabolic damage to the liver [
4]. Acetaminophen, usually referred to as paracetamol, is a well-known painkiller and fever reducing agent that causes liver and kidney toxicity. When given in a normal amount, paracetamol has no harmful effects, but a high dose can harm the liver [
5]. Acetaminophen-induced liver injury is caused by the toxic metabolite N-acetyl-p-benzoquinoneimine (NABQI), manufactured by cytochrome P-450 enzymes [
6,
7]. This substance is normally altered by conjugation with glutathione, but in a high dose this element is generated in such excessive concentrations that it overpowers the detoxification process, causing hepatocyte damage and cell death [
8]. According to [
9], different high dosages of acetaminophen showed a noteworthy increase in liver enzyme activities.
The kidneys are also important homeostatic organs [
10]. Toxic overdose of drugs leads to renal toxicity, often associated with numerous metabolic disorders such as imbalances in serum electrolytes, urea, uric acid, and creatinine [
11,
12]; these are crucial biomarkers for detecting kidney function [
13]. Reactive oxygen species (ROS) are produced in both hepatotoxicity and nephrotoxicity, and they damage the integrity of cell membranes and release cellular enzymes such as hepatic transaminases, such as (ALT), (AST), (ALP) and lactate dehydrogenase (LDH), into the bloodstream and increase levels of thiobarbituric acid reactive substances (TBARS). Other biomarkers, such as glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA), as well as haematological indices including PCV, Hb, TLC, MCH, MCHC, and MCV, are also affected by hepatocellular injury [
14,
15,
16,
17,
18]. Thus, ROS are involved in programmed cell death, which induces oxidative stress and damages biomolecules such as lipids, nucleic acids, proteins and carbohydrates [
19]. Chemo-inhibition is a method for reducing the risk of hepatotoxicity that uses both natural and synthetic substances [
20]. By restoring free radical effects to normal, antioxidant drugs contribute significantly to the prevention of oxidative damage [
21]. Numerous studies have demonstrated the powerful antioxidant capacity of medicinal plants which are rich in chemicals that scavenge free radicals [
22,
23], such as phenolic compounds, triterpenoids, flavonoids, alkaloids, and tannin [
24].
The genus
Dianthus L. belongs to the family Caryophyllaceae and comprises about 300 species distributed in Asia, Europe, North America, and Africa (Reeve, 1967). The Mediterranean region is the primary hub of genus diversity [
25,
26]. They are frequently referred to as carnations and pinks. The plants are annual, biennial or perennial.
Dianthus orientalis Adams is a herbaceous perennial plant widely distributed in southern and eastern Turkey and Asia [
27]. The plant is traditionally used as a natural cure, for example using its leaves as a diuretic and pollen as a desiccant, vulnerary, astringent, haemostatic, or diuretic [
28].
Most of world’s population relies on herbal medicine for their primary care. Herbal drugs or plant derived agents are used in combination with allopathic medicine to cure all types of diseases, including liver illness; therefore, this study aimed to investigate the curative role of the selected plant extract [
29]. As a component of Pakistani medicinal flora, aqueous extracts of
Dianthus orientalis leaves have been investigated for hepatoprotective, nephroprotective, and other serum biochemical activities. It is therefore hypothesized that this plant will give the best results regarding the healing of liver and kidney injuries induced in the laboratory and, further, should be explored based on scientific principles and should also be approved as a chief medicine in other related illnesses.
4. Discussion
Dianthus is reported to have potent antioxidant effects [
42] and anti-inflammatory and wound healing activities [
43]. However, the plant has not been well explored, which is why the present study was established for investigation.
Dianthus orientalis leaves aqueous extract (DO.AQ) was tested on paracetamol intoxicated rabbits for its antioxidant potential as well as hepatocurative and nephroprotective activities. The consumption of excessive amounts of acetaminophen (paracetamol) can damage the liver and kidneys of experimental animals, resulting in the generation of reactive oxygen species (ROS) that decimate the integrity of cell membranes, leading to cell death and imposing oxidative stress [
44]. The current study demonstrated that the consumption of paracetamol disrupted blood haematology, liver enzymes such as ALT, AST, and ALP, serum biomarkers such as urea, creatinine, and uric acid, as well as lipid profile, and also altered the histomorphological architecture, as described by [
45,
46,
47]. A similar study has been conducted by Amang et al., 2020, demonstrating that
Opilia celtidifolia is a plant used in Cameroonian ethnomedicine to cure jaundice. By reducing the levels of ALT, AST, ALP, and other serum indicators including urea, creatinine, and uric acid into the normal range, it was discovered that the (DO.AQ) extract had hepato- and nephroprotective capabilities.
Another parallel study showed that P. divaricata treatment restored altered biochemical and histopathological findings associated with PCM induced hepatotoxicity Singh, et al., 2016.
Various extract doses (100 mg/kg BW and 200 mg/kg BW) administered during the first and second treatment weeks (W1 and W2) had no noticeable impact. The high dose (400 mg/kg BW) extract, meanwhile, significantly decreased the serum enzymes by the end of the third week. Serum biochemical and histopathological status were observed to be regulated in silymarin-treated animals during the last week (W3) of study. These curative properties of (DO.AQ) extract are a result of the antioxidant activity and stabilization of the lysosomal membrane. These effects were equivalent to those of a group treated with silymarin, a standard hepatoprotective agent [
48]. A similar study was also conducted by [
49]; he studied the protective effect of
Parthenium hysterophorus against CCL4 and paracetamol-induced toxicity. Our outcomes were in line with earlier research, where Ascorbic Acid was utilized as a nephroprotective drug and paracetamol was used to cause kidney injury in animals [
50]. Serum lipids have been linked to the development of numerous heart problems. Blood contains a variety of lipids, although LDL and HDL are more important than others in terms of heart-related ailments and are more common in evaluating heart problems [
51].
According to the findings of the current study, liver damage brought on by paracetamol overdose is associated with a considerable increase in serum glucose and lipid levels, including cholesterol, TG, LDL, and a decrease in HDL [
52]. Treatment with 400 mg/kg of
Dianthus orientalis. aqueous extract has shown excellent reductions in serum glucose and lipid levels, including cholesterol, LDL, and triglyceride levels, while also increasing HDL levels. High levels of HDL cholesterol are considered to be good cholesterol as it is responsible for eradicating extra cholesterol by transporting it to the liver, thus helping prevent heart problems. For the digestion of lipids, glucose is essential. It produces pyruvic acid by glycolysis or to be converted into fatty acids, TC and TG.
The impact of paracetamol consumption is also noticeable in the animals’ haematology, where significant (
p < 0.05) reductions in the values of RBC, HB, MCV, MCH, and MCHC and an increase in WBC, PLT, lymphocyte, neutrophil, and monocyte levels were seen. Similar investigations have also been conducted, showing that hepatotoxicity might alter haematological parameters such as packed cell volume, HB, total leucocyte count (TLC), MCH, MCHC, and MCV, indicating involvement with the haematological profile [
53]. The range of harmful effects of any exogenous material, such as plant extract, on the blood composition of an animal can be ascertained through the analysis of haematological parameters [
54,
55].
Low levels of RBC, HB, MCV, MCH, and MCHC are noticeably increased by high dosages of DO.AQ extract, while WBC, PLT, lymphocyte, neutrophil, and monocyte concentrations are lowered to normal range. The normalization of these hematological parameters was observed from the third week of treatment. The high dose (400 mg/kg BW) of DO.AQ extract had a significant therapeutic effect, although the low and medium doses (100 mg/kg and 200 mg/kg BW) of the extract demonstrated no significant effect.
Dianthus orientalis leaves aqueous extract (DO.AQ) significantly enhanced haematological parameters, which may indicate that it contains phytochemicals that could stimulate the formation of erythropoietin in experimental animals’ stem cells. Erythropoietin is a glycoprotein hormone that encourages bone marrow stem cells to produce red blood cells [
56]. The results of the current investigation are consistent with those of [
57], which described how
Caulis bambusae (Bamboo) stem extract affected haematological and biochemical markers in chinchilla rabbits.
Exogenous antioxidants and the host’s own endogenous antioxidant defense system, which includes enzymatic and non-enzymatic antioxidants such as SOD, CAT, and GSH, can both prevent tissue damage brought on by oxidative stress. Reduced glutathione (GSH) is a potent nucleophilic, 3-peptide (L-γ-glutamyl cysteinyl glycine) antioxidant that is crucial for cellular defense and detoxifies reactive oxygen species by interacting with and removing harmful compounds, taking care of the inflammatory cytokine chain reactions [
58]. Reduced GSH levels in different tissues leave the body’s defenses vulnerable to reactive oxygen species (ROS), which increases the risk of peroxidative injury. According to the findings of the current investigation, paracetamol treatment decreased GSH levels in the liver and kidneys through the process of lipid peroxidation, which may have led to the production of free radicals [
59]. When compared to the control rabbits, GSH and %RSA levels in the liver and kidneys of paracetamol hepatotoxic rabbits were significantly decreased, indicating weak antioxidative defense and damage to the liver and kidneys.
Various dosages of DO.AQ extracts were administered to rabbits receiving paracetamol treatment. The levels of GSH and %RSA in the liver and kidneys were increased by a high dose extract (400 mg/kg BW), demonstrating that the plant extract’s antioxidant effect is dose dependent. A similar study was conducted by [
60], using carbon tetrachloride; they discovered a substantial decrease in liver GSH content on carbon tetrachloride ingestion. The observed reduced level of GSH in paracetamol-toxic rabbits may be related to high levels of reactive substance scavenging activity, which were triggered because of liver and renal cell necrosis and apoptosis or a potential decrease in hepatic and renal GSH synthesis. The findings of the current investigation are similar to those of [
61], which examined the protective impact of
Aerva jevanica against ethanol-induced hepatic injury in rats; he came to the conclusion that
Aerva jevanica (AJME) contained antioxidants and hepatoprotective properties. Silymarin increased the quantity of glutathione and the activity of antioxidant enzymes, whereas a dose-dependent decrease in lipid peroxidation was observed with silymarin and extracts [
62].
High amounts of the reactive oxygen species (ROS) can cause the destruction of biological molecules including lipids, proteins, and nucleic acids. Antioxidant defenses have evolved to eliminate most of these oxidant mediators in order to prevent this condition. Oxidative stress develops when the delicate equilibrium between oxidative damage and defense systems is disturbed [
63,
64], and it has been shown that high lipid peroxide concentrations increase TBARS levels in the liver and kidneys of paracetamol-fed rabbits, as TBARS is an index of lipid peroxidation. Our findings demonstrate that TBARS levels were high in the liver and kidney of paracetamol control animals because of high lipid peroxidation. The liver and kidney TBARS levels were low in animals given a high dose of
Dianthus orientalis aqueous extract. This reduction in TBARS levels may be caused by DO.AQ extracts’ active components, which may be involved in scavenging ROS and enhancing the antioxidant capacities of tissues. Our study agrees with [
65], which analyzed the oxidative stress variables in streptozotocin induced diabetic rats and treated them with piper leaf [
66,
67].
Dianthus orientalis leaves aqueous extract (DO.AQ) was tested in the current investigation for its in vitro antioxidant activity against the DPPH free radical scavenging system, since it showed some variation in the level of various pharmacological activities. The % inhibition increased as the concentration of the extract increased. This rise in % inhibition shows the antioxidant capacity of Dianthus orientalis. The exact process by which plant extracts reduce lipid peroxidation is unknown, although it is possible that their antioxidant qualities are a key factor. Alkaloids, carotenoids, and phenolic compounds are the three main chemical components of plants. Due to their antioxidant properties, these chemicals are particularly effective against acute or chronic liver and kidney disorders, comprising cancer and heart ailments.