Research Article

Effectiveness of Cinnamomum cassia against Liver and Kidney Biochemical Assay and Hematology in Bisphenol-A Induced Rats

Tehreem Iqbal1, Roheela Yasmeen1* and Faheem Hafeez2

1Lahore Garrison University, Phase VI, Sector C DHA, Lahore, Pakistan; 2Department of Biology, Lahore Garrison University, Phase IV, Sector C, Avenue IV, DHA, Lahore, Pakistan.

Received | April 11, 2023; Accepted | June 17, 2023; Published | June 28, 2023

*Correspondence | Roheela Yasmeen, Lahore Garrison University, Phase VI, Sector C DHA, Lahore, Pakistan; Email: [email protected], [email protected]

Citation | Iqbal, T. and R. Yasmeen. 2023. Effectiveness of Cinnamomum cassia against liver and kidney biochemical assay and hematology in bisphenol-a induced rats. Biologia (Lahore), 69(1): 7-14.

DOI | https://dx.doi.org/10.17582/journal.Biologia/2023/69.1.7.14

Keywords | Bisphenol-A, Cinnamomum cassia, Liver, Kidney, Antioxidant effects

Copyright: 2023 by the authors. Licensee ResearchersLinks Ltd, England, UK.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Introduction

BisphenolA (BPA) is an organic chemical commonly used in the manufacturing of polycarbonates, epoxy resins, and other polymer products as a monomer or additive. Its most important applications are the formation of polyacrylate resins, polyester resins, flame retardants, polysulfone resins, and polyethylene resin (Huang et al., 2011; Almeida et al., 2018).

Although, it is a well-studied endocrine disruptor whose toxicologic and multidirectional behavior is extensively studied (Huang et al., 2012; Björnsdotter et al., 2017). According to latest study it is a foreign xenoestrogen, that not formed naturally in living organisms but identical to normal 17 β estradiol (Kapustka et al., 2020). It was also categorized as a poor environmental estrogen that showed multidirectional toxic behavior (Liliana et al., 2019).

The studies indicated that exposure to BPA increases prostatic weight and brain activity, changes the growth, testosterone synthesis, disruption of sperm excretion, and reproductive organ development disturbance in mice (Michałowicz, 2014; Yilmaz et al., 2020). Developmental toxicity studies have also shown negative outcomes in rats at the levels or below the current acceptable daily intake levels for this compound (Rubin, 2011). The adverse effects of BPA included changes in puberty time, estrous cycles, the prostate, mammary glands growth, uterus and ovaries, brain sexual dimorphism, brain steroid receptor, sociosexualbehaviour, body weight, and glucose homeostasis (Michałowicz, 2014). Other health risks in human due to this compound are also well known such as cardiovascular illness, diabetes, increased numbers of premature births, the decrease in semen production, and sperm DNA damage (Rubin, 2011; Wu et al., 2013).

Natural plant-driven antioxidants are highly demanded than synthetic antioxidants because of their capacity for enhancing fitness, preventing diseases, protecting, and consumer acceptability (Skerget et al., 2005; Gulcin, 2006a, b; Gulcin et al., 2006c; Majhenic et al., 2007). In the present decade, the usage of herbs and spices as antioxidants and anticancer agents are being popular to overcome a numer of diseases (Embuscado, 2015). Cinnamon (Cinnamomum, Lauraceae family) is one of those spices that rich in antioxidants and phytochemical compounds (Udayaprakash et al., 2015). It is one of the most commonly used plants with diverse bioactive effects in herbal medicines (Błaszczyk et al., 2021). The Cinnamomum cassia (C. cassia) or Chinese cinnamon plant is an evergreen tall tree with dense leathery leaves and yellow flowers (Suriyagoda et al., 2021).

Due to the possible toxicity risks of BPA in different biological systems, it is important to implement less costly and non-synthetic products against BPA for the safer use of organisms. This is why bioactive compounds from different plants are exponentially used to track their viability in studies compared to synthetic ones. This study is novel as it explore valuable effects of natural products, C. cassia extracts to assess their effect against liver and kidney toxicity caused by BPA. The present research study was designed to evaluate Bisphenol-A induced toxicity in the liver of Sprague Dawley rats and its treatment with C. cassia through various bioassays like hematology, biomarkers of liver and kidney function tests.

Materials and Methods

Experimental plan

Twenty-five post-weaning male Sprague Dawley rats of similar weight were divided into five groups (control + treated). The Sprague Dawley rats were kept in steel cages according to standard conditions (temperature, 25°C; humidity, 45–65%; light/dark cycle, 12 h/12 h). The rats were provided with open access to water and food. The experimental study was designed for 30 days and included Bisphenol A (BPA) induced subacute toxicity in Sprague Dawley rats and its amelioration by Cinnamomum cassia (C. cassia) effective dose (225 mg/kg) from the previously reported study of Iqbal et al. (2020). BPA dose was based on previously reported LD50 of BPA (3250 mg/kg body weight) Furuya et al. (2006).

Grouping of rats

The study was allocated into two major groups (control and treated). A control group was further divided into a negative control group (C) that was remained untreated and only administrated with commercial feed and water. A vehicle control group (P) was fed olive oil (1m) for equivalency of shock (to see any toxic effect of olive oil as Bisphenol-A was dissolved in olive oil to prepare the dose for the treatment groups ). A BG1 (positive) group that was treated with only Bisphenol-A.

A treated group was divided into two groups that were fed on selected doses of C. cassia for 3 days per week. One was the CG2 group that was pretreated with C. cassia (225 mg/kg per BW of rat) 24 hours before the administration of Bisphenol-A and CG3 that were post-treated with C. cassia after 24 hours of the administration of Bisphenol-A.

After 30 days, the rats were sacrificed and selected samples were collected for the biochemical assay (liver and kidney function tests) and hematology.

Source of bisphenol A and C. cassia

BPA was purchased from sigma Aldrich (CAS80-05-7) and C. cassia bark was purchased from local market of Faisalabad an further be confirmed by Department of botany from Goveronment College University Faisalabad.

Preparation of C. cassia extract

C. cassia was prepared with slight modifications in the methodology of Dahal et al. (2017). For this 500 grams of dried and crushed C. cassia bark were mixed with methanol and kept for 15 days at room temperature. After 15 days solution was filtered by Whatman No.1 filter paper and dried at room temperature. The extracts were stored in dark at room temperature (Dahal et al., 2017).

Liver function tests

To study the potential toxicities of the BPA, the biochemical parameters such as Total bilirubin (TB), alkaline phosphate test (ALP), Lactate dehydrogenase (LDH), and alanine aminotransferase (ALT) of blood samples were determined by using commercially available assay kit and following the instruction of the manufacturer.

Kidney function test

For kidney function biomarkers such as creatinine(CRT), blood urea nitrogen (BUN) and uric acid (UA) tests were performed.

Hematological analysis of blood

For CBC analysis blood samples were collected through caudal puncture of animals in the tubes that contained calcium EDTA. By using a hematology auto-analyzer blood parameters such as hemoglobin (HB), red blood cells (RBCs), hematocrit (HCT), mean corpuscles volume (MCV), mean corpuscles hemoglobin (MCH), mean corpuscles hemoglobin concentration (MCHC), white blood cells (WBCs), and platelets (PLT) were determined for each control and treated groups.

Results and Discussion

Impact of BPA on relative weight and histoarchitecture of liver

The relative weight of the liver were weighed after BPA administration. A significant increase was noticed in the liver weight in experimental groups as compared to control (Figue 1).

 

Biomarkers of liver function

The biomarkers of liver test total bilirubin (TB), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and alanine transaminase (ALT) were recorded after 30 days. A statistically significant (p< 0.05) differences were noticed in the TB, ALP, LDH, and ALT of the control and experimental groups (Figure 2). An overall increase in liver biomarkers such as TB, ALP, LDH, and ALT were recorded only in BPA treated rats rather than C and P control groups. The biomarkers of liver function were highly improved in C. cassia treated groups although the maximum improvement were recorded in pretreated rats as compared to post treated rats.

 

Biomarkers of Kidney function

The biomarkers of renal function such as blood urea nitrogen (BUN), creatinine (CRT), and uric acid (UA) were found significantly higher (p< 0.05) in BPA-treated rats than the control rats (C and P) (Table 1). The levels of biomarkers of kidney function were restored in C. cassia-treated groups (CG2 and CG3) although the maximum improvement was observed in pre-treated rats as compared to post-treated rats.

 

Table 1: Biomarkers of kidney function test in control and treated groups.

Groups	BUN (IU/L)	CRT (g/dl)	UA (g/dl)
C	67.34+0.03C	0.504+0.05C	2.91+0.06C
P	67.80+0.266C	0.506+0.05C	3.10+0.023C
BG1	89.41+0.19A	0.851+0.03A	5.53+0.03A
CG2	69.01+0.38BC	0.526+0.03BC	3.58+0.03BC
CG3	71.22+0.23B	0.576+0.05B	4.01+0.05B

 

The results were expressed as Mean ± SD; means with different letters in the column are significantly different at p<0.05.

 

Hematological analysis

The hematological analysis of Sprague Dawley rats that recorded after 30 days and shown in Table 2. The hemoglobin (HB) and red blood cells (RBCs) were decreased significantly (p < 0.05) in only BPA treated group (BG1) than the control groups (C and P). The RBCs and HB indices such as mean corpuscles hemoglobin (MCH), hematocrit (HCT), mean corpuscular hemoglobin concentration (MCHC), and mean corpuscular volume (MCV) were also reduced significantly (p < 0.05) in the BG1 group. White blood cells (WBCs) and Platelets (PLTs) were elevated significantly (p<0.05) in the BG1 (only BPA treated rats) group. The RBCs, HB, along with their indices were improved in both groups (CG2, and CG3) C. cassia pre-treated and post-treated rats than only BPA treated groups. The levels of WBCs and PLTs were also restored after C. cassia supplementation in pre-treated and co-treated groups. However, maximum improvements were observed in C.cassia pre-treated group (CG2).

BPA is absorbed rapidly upon its exposure to the biological system and imposes significant impacts on animals. Its bioavailability is poorer after oral administration than subcutaneous exposure (Almeida et al., 2018). It is absorbed in the gastrointestinal tract and transferred to the liver, where it is metabolized by glucuronidation and sulfation to produce inactive forms of BPA. In human fluids and tissues, its unconjugated or free forms with estrogenic activity are comparatively low (ng/mL) due to its natural similarity to natural estrogen hormone (Soriano et al., 2016). Antioxidants slow or prevent lipid or other molecule oxidation by preventing the initiation or proliferation of oxidizing chain reactions (Velioglu et al., 1998). Free radicals are absorbed and neutralized, singlet and triplet oxygen (Osawa, 1994).

In the present research study Sprague Dawley rats were used to measure the toxic impact of BPA and its amelioration was done by C. cassia at an effective natural product. An increase in liver weight was noticed in BPA exposed rats in previous study and similar findings were noticed in the present study (Yıldız and Barlas, 2013). The relative weight of the liver BPA- treated rats was observed higher as compared to the control, which marks the liver injuries. Furthermore, this significant increase in serum concentration might be due to liver enzymatic and non-enzymatic biomarkers that leads to changes in the liver structure like infiltration of inflammatory cells, change in mitochondrial ATPase activity and congestion in liver cells which are chief factors that brought about a decrease in the relative liver weight (Hassan et al., 2012; Iqbal et al., 2021). While C. cassia supplementations either pretreated (only C. cassia) or post-treated (BPA+ C.cassia) improved the relativeiver weight in rats. These findings were corroborated with results of Morgan et al. (2014) who reported

 

Table 2: Blood biochemistry in treated and control groups.

Groups	HB	RBCs (106/mm3)	HCT (%)	MCV (fl)	MCH (pg)	MCHC (g/dl)	WBCs (103/mm3)	PLT (103/ mm3)
C	16.076+ 0.16A	8.128+ 0.15A	46.508+ 0.6A	56.9+ 0.2A	18.058+ 0.09A	38.106+ 0.68A	16.058+ 0.15D	923.8+ 2.7D
V	15.998+ 0.10A	8.086+ 0.10A	46.402+ 0.59A	56.78+ 0.44A	18.054+ 0.09A	38.082+ 0.72A	16.016+ 0.4D	923.6+ 2.4D
BG1	13.156+ 0.12C	6.404+ 0.2C	39.88+ 0.43D	47.992+ 0.81D	14.352+ 0.2D	31.848+ 0.49D	20.156+ 0.14A	1100+ 1.5A
CG2	15.912+ 0.14B	8.024+ 0.1B	46.062+ 0.97B	56.184+ 0.34B	17.832+ 0.4B	37.822+ 0.79B	17.97+ 0.11C	924.43+ 2.73C
CG3	15.126+ 0.11C	7.862+ 0.2BC	45.644+ 1.3C	55.244+ 0.82C	16.926+ 0.28C	36.886+ 0.78C	18.32+ 0.24B	925.83+ 1.64B

 

Values are presented as mean ± S.D. (n = 5 animals/group).Means that do not share the same letter are significantly different in column at p<0.05

 

C. cassia supplementations before and after octylphenol treatments helped to restore relative organ weight and body weight due to the improvement of various biochemical alterations in rats.

The occurrence of liver injury or inflammation was assessed by the liver function tests including ALP, ALT, TB, and LDH. The liver profile revealed biochemical improvements, with a considerable (p<0.05) rise in liver biomarkers in the BG1 group (only treated with BPA) compared to those of the control group. The results of our research showed that a high dose of BPA dramatically increased the serum indices of liver function, whereas the lower dosage groups were close to average. In our findings both ALT and ATP were found higher while high levels of ALP are linked to liver injury and ALT not found affected by the study of Tsung et al. (2019). Similarly elevated levels of serum indices for liver damage were previously identified in rats exposed to 30 mg BPA/kg/day, with no symptoms at less than 5 mg (Hassan et al., 2012). A similar research found that BPA participants had higher serum ALT levels than the test group (Korkmaz et al., 2010). C. cassia pretreatments and co-treatment (225 mg/kg per BW of rat) with BPA restored the liver profile including enzymatic and non-enzymatic biomarkers. Previous studies reported that C.cassia exert a protective effect owing to the presence of phytoconstituents such as flavonoid and phenolic contents that assist to scavenge free radicals and reduce oxidative stress which is the primary mechanism of action. The antioxidant level ultimately increases that helped to improve the liver and kidney profiles (Hassan, 2022).

The result of the renal function test indicated a considerable elevation of (BUN, CRT, and UA) in the BG1 group (only BPA treated-rats) than other groups. BPA was reported to induce hyperglycemia, which could cause kidney damage and renal dysfunction, thereby significantly increasing serum urea, creatinine, and uric acid (El-Yamani, 2011). After the treatment of C. cassia bark methanolic extract, either pre-treatment or post-treatment with BPA helped to restore the normal renal profile of rats. Although the best results were found in C. cassia (225 mg/kg) pre-treated rats. Previous research by Iqbal et al. (2020) found consistent with our study who observed that C. cassia treatments at various doses (175, 225, and 200 mg/kg B.W) reduced CRT, UA, and BUN levels after Ni nanoparticles induced renal toxicity in rats (Iqbal et al., 2020).

The findings of the hematological analysis showed a considerable (p<0.05) reduction of HB and RBCs only in the BPA exposed group which marked anemia. The anemia may be due to the lysis of blood cells or decrease in haemoglobin (Lukose et al., 2019; Hoque et al., 2020). The blood lysis after the treatment with bisphenol A was might be due to oxidative stress-induced cell and membrane damage in erythrocytes of rats (Suthar et al., 2014). The significant (p<0.05) production of platelets and WBCs were observed in the BG1 group because of the immunogenic response to deal with infectious conditions after BPA exposure (Srivastava and Reddy, 2020). It was reported in literature that high levels of BPA administration gradually increased the degree of cellular infiltration and the number of Kupffer cells (Verma and Sangai, 2009; Kamel et al., 2018). However, C. cassia pretreatments and post-treatments (BPA+ C. cassia) improved the RBCs and HB levels as well as their indices (HT, MCV, MCH, and MCHC). WBCs and PLTs were also significantly decreased in C. cassia (225 mg/kg per BW of rat) pretreated and post-treated groups. It was also reported that usage of C. cassia improved the hematological parameters in various in vivo studies and they suggested the surplus polyphenol and flavonoids components assisted to scavenge free radicals that are coherent with blood cell lysis (Iqbal et al., 2020; Shakeel et al., 2018).

Conclusions and Recommendations

It was concluded that BPA at 225 mg/kg/BW caused adverse effects on the exposed animals after oral administration as evidenced by the change in blood biochemistry, liver and kidney profile. Besides, the relative weight of the liver was decreased after BPA exposure. C. cassia treatments improved all the parameters and pretreatments played a prominent defensive function against such side effects as compared to post trreatments.

Conflict of interest

The authors have declared no conflict of interest.

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