Protective mechanisms of protocatechuic acid against doxorubicin-induced nephrotoxicity in rat model

Author(s):  
Olorunfemi R. Molehin ◽  
Anne A. Adeyanju ◽  
Stephen A. Adefegha ◽  
Ajibade O. Oyeyemi ◽  
Kehinde A. Idowu

AbstractBackgroundDoxorubicin (DOX) induces toxicity in many tissues/organs, including the heart, kidney and so on. This study was designed to evaluate the modulatory effects of protocatechuic acid (PCA) against DOX-induced nephrotoxicity in rats. Animals were randomly grouped into five groups.MethodsGroup 1 served as the normal control (CTR). A single dose of DOX at 20 mg/kg was administered intraperitoneally (i.p.) to animals in Group 2. Groups 3 and 4 were pretreated with PCA for 5 days (doses of 10 and 20 mg/kg body weight, respectively) after which DOX was injected (PCA-10 + DOX and PCA-20 + DOX). Group 5 received PCA only at a dose of 20 mg/kg body weight (PCA-20).ResultsThe results revealed significant elevations (p < 0.05) in malondialdehyde content, expressions of inducible nitric oxide (iNOS) and cyclooxygenase-2 (COX2) in the kidney. Likewise, increased serum levels of creatinine and urea of DOX group were observed. A significant decrease (p < 0.05) in glutathione (GSH) level and antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione s- transferase (GST) activities in the kidney were observed compared with the control. Pretreatment with PCA (10 and 20 mg/kg, p.o.) for 5 days prior to the i.p. injection of DOX reduced MDA levels, modulated iNOS and COX2 activities and improved kidney function markers as well as oxidative stress parameters. Findings from the histopathology studies confirms the protective effects of PCA on DOX-induced damage on the kidney cells.ConclusionsThis study has demonstrated the anti-inflammatory and antioxidative properties of PCA, which could be part of its possible protective mechanisms against nephrotoxicity induced by DOX.

2019 ◽  
Vol 36 (1) ◽  
pp. 38-47
Author(s):  
Rotimi O. Arise ◽  
Abimbola K. Arise ◽  
Oluwole I. Oyewole ◽  
Sylvia O. Malomo

Summary Monosodium glutamate (MSG), an established excitotoxic food additive, has been found to induce oxidative stress in all tissues. To examine the protective effects of ivermectin on MSG-induced excitotoxicity, 28 male albino rats were randomized into four groups. Group 1, the control, received 1 ml of oral distilled water, group 2 was administered an aqueous solution of MSG (4 mg/kg body weight/day). Group 3 was co-administered with the same dose of MSG and 0.4 mg/kg body weight of ivermectin, while group 4 rats received orally the same dose of MSG for 2 weeks, after which ivermectin was administered orally for 1 week. Administration of MSG orally for 21 days and for 14 days, followed by oral administration of ivermectin for 7 days, significantly increased (p < 0.05) glutathione-S-transferase, nitric oxide synthase, superoxide dismutase and catalase activities as well as malondialdehyde and intracellular Ca2+ concentrations while Na+ - K+ - ATPase, Ca2+ - Mg2+ - ATPase, acid phosphatase (ACP) and alkaline phosphatase (ALP) activities were significantly reduced (p < 0.05) compared to the control. However, co-administration of MSG and ivermectin for 21 days did not show any significant difference (p > 0.05) in all the parameters studied compared to the control. This result suggests that ivermectin may protect against MSG-induced excitotoxicity in rats.


2021 ◽  
Vol 13 (2) ◽  
pp. 616-626
Author(s):  
Dharmender Sharma ◽  
Gurinder Kaur Sangha

The present investigation was carried out to assess the antioxidative potential of Broccoli sprouts aqueous extract (BE) against triazophos (TZ) induced oxidative stress (OS) in brain and spleen. In the experimental setup, six groups of rats were formed; Control (group 1), BE (group 2), TZ (group 3), and also BE+TZ groups such as BE1 (group 4), BE2 (group 5) and BE3 (group 6) groups. Rats were orally intubated for 30 days as per experimental design. After sacrifice, OS biomarkers viz; catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and lipid peroxidation (LPO) levels were determined in brain and spleen. Acetylcholinesterase (AChE) activity was observed in plasma and brain samples. Histological study of the spleen in TZ rats showed increased thickness of capsule, congestion and hypocellularity in follicles of spleen’s white pulp and the histoarchitecture was restored in TZ+BE group rats. TZ caused degenerative changes in brain histology and rats showed mild congestion along with haemorrhage in the cerebral cortex. Results suggest that TZ exposure is associated with neural toxicity along with altered spleen stress biomarkers, which further corroborates with histopathological findings. It is inferred that BE exerts multi-mechanistic protective effects against TZ induced neuro-splenic toxicity which is attributable to its protective antioxidant actions.


2016 ◽  
Vol 43 (5) ◽  
pp. 348-353 ◽  
Author(s):  
IGOR NAGAI YAMAKI ◽  
RUY VICTOR SIMÕES PONTES ◽  
FELIPE LOBATO DA SILVA COSTA ◽  
VITOR NAGAI YAMAKI ◽  
RENAN KLEBER COSTA TEIXEIRA ◽  
...  

ABSTRACT Objective: to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. Methods: we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. Results: The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Conclusion: Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning.


Author(s):  
Shamsi NOORPISHEH GHADIMI ◽  
Leila HOMAYOON ◽  
Reza SHAHRIARIRAD ◽  
Shakila FATEHPOUR ◽  
Mohammad RASTEGARIAN ◽  
...  

Background: The current study aimed to investigate the possible cross-protective effects of attenuated L. major against L. infantum in BALB/c mice. Methods: This experimental study was performed in 2017 in Shiraz University of Medical Sciences, Shiraz, Iran. The attenuated strain of L. major was prepared by continuous weekly subculturing of the parasite. Forty-eight female BALB/c mice were divided into eight groups. Group 1 injected (ID) with wild type of L. major; group 2 injected (IV) with L. infantum; group 3 injected (ID) with attenuated L. major; group 4 injected (ID) with attenuated L. major, and after three weeks challenged (IV) with L. infantum; group 5 injected (IP) with attenuated L. major; group 6 injected (IP) with attenuated L. major, and challenged (IV) with L. infantum (IV); group 7 injected (IV) with attenuated L. major; and finally group 8 injected (IV) with attenuated L. major and after three weeks challenged (IV) with L. infantum. Forty-five days post-infection, the parasite load in the spleen and liver of the mice was determined as Leishman-Donovan units (LDU). Results: The differences in mean of LDU of spleen between different groups were statistically significant (P<0.048). In addition, the differences in percent of infection in liver between pairwise comparisons of groups were statistically significant (P<0.05). The highest intensity of infection was observed in group 2 while low intensity of infection was seen in groups 3, 4 and 5. Conclusion: Live attenuated L. major can induce substantial protection against L. infantum, particularly when the parasites were injected intravenously.


2020 ◽  
Vol 245 (16) ◽  
pp. 1490-1503 ◽  
Author(s):  
Adedoyin O Adefisan ◽  
Judith C Madu ◽  
Solomon E Owumi ◽  
Oluwatosin A Adaramoye

Reproductive dysfunction stemming from chemical agents may lead to infertility. We examined the protective effects of Calliandra portoricensis ( CP) extract on benzo[a]pyrene (BaP) and N-methyl- N-nitrosourea (NMU)-induced ovarian and uterine toxicity in rat, treated as follows: control (group 1), NMU + BaP (group 2), groups 3 and 4 received (NMU + BaP), and CP (50 and 100 mg/kg), respectively. Group 5: CP (100 mg/kg) alone, group 6: (NMU + BaP) and vincristine (VIN: 0.5 mg/kg) and group 7: VIN alone. Rats were injected at age 7, 10, and 13 weeks with single doses of NMU and BaP for 10 consecutive weeks. NMU + BaP significantly ( P < 0.05) increased ovarian and uterine weight, and decreased bodyweight, while the organo-somatic index (OSI) of uterus and ovary increased 2.3 and 1.4 folds, respectively. CP co-treatment ameliorated the observed weight changes. Lipid peroxidation increased by 58% in the ovary, accompanied by decreases in ovarian and uterine GST, GPx, catalase activities, and total sulfhydryl level in NMU + BaP-treated rats. Uterine and ovarian myeloperoxidase activities, as well as nitric oxide levels also increased. CP co-treatment ameliorated the observed changes in antioxidant enzymes and inflammatory biomarkers. Furthermore, histopathology revealed fibrotic ovarian stroma, while uterine endometrium was infiltrated with inflamed cells. Immunohistochemistry showed weak expression of FSH, LH, p53, caspase-3, and Bax, whereas progesterone, iNOS, and Bcl-2 were strongly expressed in NMU + BaP-treated rats. CP treatment restored the architecture of these tissues. Conclusively, the root bark fraction of CP decreases oxido-inflammatory damage in ovarian and uterine tissues of NMU- and BaP-treated rats. Impact statement Infertility resulting from reproductive impairment is traumatic in families. Exposure to chemicals may play insidious roles not easily connected to infertility. We examined benzo[a]pyrene (BaP), and N-methyl nitrosourea (NMU)-induced ovarian and uterine toxicity and the role of Calliandra portoricensis in mitigating toxicity. In a bid to illuminate folk medical claims cloaked in mystery, unearthing lost knowledge, advance natural chemopreventive agents, and report new evidence lacking in the literature attributed to CP. Although CP is known to exhibit anticonvulsant, antidiarrheal, antipyretic, antirheumatic, and analgesic effects in humans, its possible roles for mitigating toxicity stemming from inadvertent chemical exposures are reported here. Our findings affirm and further show that CP abates toxic response incumbent on oxidative damage and inflammatory responses associated with NMU and BaP exposure. Development of phytochemical derived from CP may serve as a potential natural therapy against chemical toxicities in individuals inadvertently exposed, and promote human health and reproductive satiety.


2021 ◽  
Vol 1 (1) ◽  
pp. 014-022
Author(s):  
Omodamiro O.D. ◽  
Alaebo P.O. ◽  
Olukotun B.G. ◽  
Chikezie P.C.

Gongronema latifolium is highly medicinal in nature. The fundamental ingredients used for medicinal purposes are stored in the various parts of the plant such as the fruits, seeds, leaves, root and stem. This present study is aimed to evaluate the hepatotoxicity effect of methanolic leaf extract of Gongronema latifolium on albino rats. This study was divided into five groups normal control groups: received commercial rat feed and water, group 2: received 1000 mg/kg b.w. of leaf extract of Gongronema latifolium, group 3: received 500 mg/kg b.w of leaf extract of G. latifolium, group 4; received 250 mg/kg of leaf extract of Gongronema latifolium, and group 5: received 125mg/kg of leaf extract of Gongronema latifolium. The result shows a significant (p<0.05) increase in serum levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total and conjugate bilirubin when compared to the normal control not giving the extract. Administration graded dosage of 1000mg/kg and 500mg/kg body weight significantly (p<0.05) increased the liver damage marker enzymes when compared with groups that received low dosage of 250mg/kg and 125mg/kg body weight and the normal control groups. The histopathological study revealed severe portal inflammation without steatosis and moderate portal inflammation in groups that received 1000mg/kg and 500mg/kg. Therefore, these results suggested that methanol leaf extracts of Gongronema latifolium possess hepatotoxic properties and strict caution must be observed when using the plant extract as a natural remedy of any disease.


2006 ◽  
Vol 25 (5) ◽  
pp. 235-242 ◽  
Author(s):  
Tamanna Jahangir ◽  
Tajdar Husain Khan ◽  
Lakshmi Prasad ◽  
Sarwat Sultana

Excess iron deposition in tissues leads to organ dysfunction and impairment. In this study, the protective effects of farnesol (FL), an isoprenoid, against Fe-NTA (9 mg iron/kg body weight i.p.)-induced oxidative damage and early tumour promotion markers are evaluated. The pretreatment of iron-intoxicated rats with 1% and 2%/kg body weight oral dose of FL for 7 consecutive days significantly reversed the iron-induced increase in H2O2 content (P <0.001), malondialdehyde formation, xanthine oxidase activity (P <0.001), ornithine decarboxylase activity (P <0.001) and 3[H]thymidine incorporation in renal DNA (P <0.005) with simultaneous significant depletion in serum toxicity markers blood urea nitrogen (BUN) and creatinine (P <0.001). Significant dose-dependent restoration was recorded in renal glutathione content, its dependent enzymes and other phase II metabolizing enzymes viz., catalase, glutathione-S-transferase and quinone reductase (P <0.001) with prophylactic treatment of FL. Present results support that FL markedly lowers the oxidative damage and appearance of tumour markers, which precludes its development as a chemopreventive tool.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Anna Roosdiana ◽  
Fajar Shodiq Permata ◽  
Riera Indah Fitriani ◽  
Khairul Umam ◽  
Anna Safitri

Ruellia tuberosa L. is a therapeutic plant that is generally consumed in Indonesian traditional medicine to prevent or cure various illnesses, i.e., diabetes. The current study was conducted to investigate the effects of hydroethanolic root extracts of Ruellia tuberosa L. on the kidney of streptozotocin-induced diabetic Wistar rats. In this study, male Wistar rats were divided into 5 groups: healthy rats (group 1), diabetic rats (group 2), and treated rats which received extract at dosages of 250 (group 3), 375 (group 4), and 500 (group 5) mg/kg body weight for 21 days. Diabetes mellitus was experimentally induced by the administration of five doses of streptozotocin 20 mg/kg body weight within five consecutive days. Significant increases in the value of TNF alpha expression and malondialdehyde (MDA) levels were observed in streptozotocin-induced diabetes rats. Furthermore, severe histological alterations of kidney tissues occurred in the diabetic rats group. After treatment was applied, the value of TNF alpha expression and MDA levels on the kidney decreased considerably p < 0.05 in groups 3, 4, and 5. The optimum dosage was obtained at a dose of 250 mg/kg body weight (group 3), which had 42.24% and 52.70% decrease in TNF alpha expression and MDA levels, respectively. The histopathological profiles of the kidney also showed significant improvements in treated groups. The most prominent recoveries were also shown in group 3. The treatments induced repairment in the glomerular and renal tubular damages in the kidney tissues. To conclude, these results emphasize potentially health valuable properties of hydroethanolic root extracts of R. tuberosa L. in rats with streptozotocin-induced diabetes.


Author(s):  
Suresh Babu Sayana ◽  
Yamuna Sampathirao ◽  
Baswaraj Munge ◽  
Sachidananda Moorthy ◽  
Kodandaramu Burli

Background: Skeletal muscle relaxants are a heterogeneous group of drugs. As a group, they are structurally and pharmacologically diverse. Skeletal muscle relaxants are usually used as adjunct therapy when initial therapy fails. They are commonly used to treat fibromyalgia, low back pain, neck pain, tension head ache, myofascial pain and muscle spasm.Methods: There were 28 mice were randomly divided into seven groups, each group consists of 4 mice. Group 1(Control): Mice were treated with normal saline and placed on rotating rod with a speed of 18 rpm (ideal speed). Group 2 (Standard-S1): Mice were treated with Nitrazepam at the dose of 2mg/kg body weight and placed on rotating rod. Group 3 (Standard-S2): Mice were treated with Nitrazepam at the dose of 3mg/kg body weight and placed on rotating rod. Group 4 (Standard-S3): Mice were treated with Nitrazepam at the dose of 4mg/kg body weight and placed on rotating rod. Group 5 (Test-T1): Mice were treated with Thiocolchicoside at the dose of 2mg/kg body weight and placed on rotating rod. Group 6 (Test-T2): Mice were treated with Thiocolchicoside at the dose of 3mg/kg body weight and placed on rotating rod. Group 7 (Test-T3): Mice were treated with Thiocolchicoside at the dose of 4mg/kg body weight and placed on rotating rod.Results: In this model inter drug comparisons were carried out with nitrazepam and thiocolchicoside. It was found that both nitrazepam and thiocolchicoside produced central muscle relaxant effect when assessed by rotarod. On iter drug comparision of nitrazepam and thiocolchicoside it was found that by increasing concentration of drug, increased the muscle relaxant property.Conclusions: When assessed by rotarod, it was found that both nitrazepam and thiocolchicoside demonstrated muscle relaxant property but with increased doses of thiocolchicoside produced more muscle relaxant property than the increase in doses of nitrazepam.


2020 ◽  
Vol 71 (11) ◽  
pp. 101-110
Author(s):  
Tayyeba Ramzan ◽  
Bilal Aslam ◽  
Faqir Muhammad ◽  
Muhammad Naeem Faisal ◽  
Asif Hussain

Ocimum sanctum L. is widely used as traditional remedy to manage hyperglycemia. This study was aimed to evaluate the effect of aqueous-methanolic extract of O. sanctum leaves (OSE) on the anti-diabetic activity of gliclazide in alloxan-induced diabetes in Wistar rats. Diabetes was induced by intraperitoneally injecting alloxan (120 mg/kg b.w.) in rats. Treatments including OSE (100 mg/kg b.w.), gliclazide (100 mg/kg b.w.), and in combination were given daily to diabetic rats till the 21st day of study. Body weight and fasting blood glucose levels were determined at regular intervals, while blood and organ samples were taken at the end of the study for biochemical and histopathological studies. Results showed that treatments exhibited anti-hyperglycemic activity through significantly (p [ 0.05) restoring body weight, fasting blood glucose level, and serum levels of glucose, insulin and HbA1c. The anti-lipidemic activity was noticed as total cholesterol (TC), triglyceride (TG), high-/low density-lipoproteins (HDL-C, LDL-C) levels were restored in treated diabetic rats. Ameliorative effects of treatments were observed as significant (p [ 0.05) reduction in serum levels of liver function biomarkers (alanine aminotransferase; ALT, aspartate aminotransferase; AST, alkaline phosphatase; ALP and bilirubin; BIL) and restoration of oxidative stress biomarkers (catalase; CAT, superoxide dismutase; SOD and malondialdehyde; MDA) in liver tissue. Histopathological findings supported these results as an increase in pancreatic islets size and protective effects on liver tissue was observed in diabetic rats treated with gliclazide and OSE alone and their combination. Conclusively, the combination of OSE and gliclazide produced a synergistic anti-diabetic effect as compared to that of alone treatment.


Sign in / Sign up

Export Citation Format

Share Document