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Article ; Online: Simvastatin mitigates diabetic nephropathy by upregulating farnesoid X receptor and Nrf2/HO-1 signaling and attenuating oxidative stress and inflammation in rats.

Hasan, Iman H / Shaheen, Sameerah Y / Alhusaini, Ahlam M / Mahmoud, Ayman M

2024 Volume 340, Page(s) 122445

Abstract: Diabetic nephropathy is one of the complications of diabetes that affects the kidney and can result in renal failure. The cholesterol-lowering drug simvastatin (SIM) has shown promising effects against diabetic nephropathy (DN). This study evaluated the ... ...

Abstract	Diabetic nephropathy is one of the complications of diabetes that affects the kidney and can result in renal failure. The cholesterol-lowering drug simvastatin (SIM) has shown promising effects against diabetic nephropathy (DN). This study evaluated the protective role of SIM on DN, pointing to the involvement of farnesoid X receptor (FXR) and Nrf2/HO-1 signaling in attenuating inflammatory response, oxidative injury, and tissue damage in streptozotocin-induced diabetic rats. SIM was supplemented orally for 8 weeks, and samples were collected for analysis. SIM effectively ameliorated hyperglycemia, kidney hypertrophy, body weight loss, and tissue injury and fibrosis in diabetic animals. SIM mitigated oxidative stress (OS), inflammatory response, and cell death, as evidenced by the suppressed malondialdehyde, nitric oxide, myeloperoxidase, NF-kB, TNF-α, IL-1β, CD68, Bax, and caspase-3 in the diabetic kidney. These effects were linked to suppressed Keap1, upregulated FXR, Nrf2, and HO-1, and enhanced antioxidant defenses and Bcl-2. The in silico findings revealed the binding affinity of SIM with NF-kB, caspase-3, Keap1, HO-1, and FXR. In conclusion, SIM protects against DN by attenuating hyperglycemia, kidney injury, fibrosis, inflammation, and OS, and upregulating antioxidants, FXR, and Nrf2/HO-1 signaling.
MeSH term(s)	Rats ; Animals ; Diabetic Nephropathies/metabolism ; NF-E2-Related Factor 2/metabolism ; Kelch-Like ECH-Associated Protein 1/metabolism ; Caspase 3/metabolism ; NF-kappa B/metabolism ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/drug therapy ; Diabetes Mellitus, Experimental/metabolism ; Simvastatin/pharmacology ; Simvastatin/therapeutic use ; Kidney/metabolism ; Oxidative Stress ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Inflammation/pathology ; Hyperglycemia/metabolism ; Fibrosis
Chemical Substances	NF-E2-Related Factor 2 ; Kelch-Like ECH-Associated Protein 1 ; Caspase 3 (EC 3.4.22.-) ; NF-kappa B ; Simvastatin (AGG2FN16EV) ; Antioxidants
Language	English
Publishing date	2024-01-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2024.122445
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Article ; Online: Acetyl-L-Carnitine and Liposomal Co-Enzyme Q

Alhusaini, Ahlam M / Alsoghayer, Rahaf / Alhushan, Lina / Alanazi, Abeer M / Hasan, Iman H

International journal of molecular sciences

2023 Volume 24, Issue 14

Abstract: Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. ... ...

Abstract	Propionic acid (PRA) is a metabolic end-product of enteric bacteria in the gut, and it is commonly used as a food preservative. Despite the necessity of PRA for immunity in the body, excessive exposure to this product may result in disruptive effects. The purpose of this study is to examine the hepatoprotective effects of acetyl-L-carnitine (A-CAR) and liposomal-coenzyme Q
MeSH term(s)	Rats ; Animals ; Acetylcarnitine/pharmacology ; Ubiquinone/pharmacology ; Oxidative Stress ; Apoptosis ; Fibrosis ; Inflammation/drug therapy
Chemical Substances	Acetylcarnitine (6DH1W9VH8Q) ; propionic acid (JHU490RVYR) ; Ubiquinone (1339-63-5)
Language	English
Publishing date	2023-07-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241411519
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Article ; Online: Roles of Nrf2/HO-1 and ICAM-1 in the Protective Effect of Nano-Curcumin against Copper-Induced Lung Injury.

Sarawi, Wedad S / Alhusaini, Ahlam M / Alghibiwi, Hanan K / Alsaab, Juman S / Hasan, Iman H

International journal of molecular sciences

2023 Volume 24, Issue 18

Abstract: Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This ... ...

Abstract	Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This work investigated the effects of curcumin (Curc) and nano-curcumin (nCurc) against Cu-induced lung injury, accenting the roles of oxidative stress, inflammation, and the nuclear factor erythroid 2-related factor/heme oxygenase-1 Nrf2/HO-1 pathway. Rats were challenged with 100 mg/kg of copper sulfate (CuSO
MeSH term(s)	Animals ; Rats ; Acute Lung Injury/pathology ; Copper/adverse effects ; Curcumin/pharmacology ; Heme Oxygenase-1/metabolism ; Inflammation/pathology ; Intercellular Adhesion Molecule-1/metabolism ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress
Chemical Substances	Copper (789U1901C5) ; Curcumin (IT942ZTH98) ; Heme Oxygenase-1 (EC 1.14.14.18) ; Intercellular Adhesion Molecule-1 (126547-89-5) ; NF-E2-Related Factor 2
Language	English
Publishing date	2023-09-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241813975
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Article: Involvement of Nrf2, JAK and COX pathways in acetaminophen-induced nephropathy: Role of some antioxidants.

Alqahtani, Qamraa H / Fadda, Laila M / Alhusaini, Ahlam M / Hasan, Iman H / Ali, Hanaa M

Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society

2023 Volume 31, Issue 10, Page(s) 101752

Abstract: Objectives: Acetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its ... ...

Abstract	Objectives: Acetaminophen (APAP)-induced nephrotoxicity is detrimental consequence for which there has not been a standardized therapeutic regimen. Although, N-acetylcysteine (NAC) is a well-known antidote used in APAP-induced hepatotoxicity, its benefit in nephrotoxicity caused by APAP is almost lacking. This study aimed to compare the possible protective effect of thymoquinone (TQ), curcumin (CR), and α-lipoic acid (α-LA), either in solo or in combination regimens with that of NAC against APAP-induced renal injury. Design and method: Rats were divided into nine groups; control group, APAP intoxicated group (1000 mg/kg; orally), and the remaining seven groups received, in addition to APAP, oral doses of NAC, TQ, CR, α-LA, CR plus TQ, TQ plus α-LA, or CR plus α-LA. The first dose of the aforementioned antioxidants was given 24 h before APAP, and then the second dose was given 2 h after APAP, whereas the last dose was given 10 h after administration of APAP. Results: Treatment with APAP elevated kidney markers like serum uric acid, urea, and creatinine. In addition, it increased the serum level of tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and thiobarbituric acid reactive species (TBARS). Also, the protein expression of renal janus kinase (JAK) and cyclooxygenase (COX)-2 were all upregulated by APAP. In contrast, the expression of Nrf2 and the renal levels of superoxide dismutase and glutathione were downregulated. Treatment with the indicated natural antioxidants resulted in amelioration of the aberrated parameters through exhibiting anti-inflammatory, antioxidant and free radical-scavenging effects with a variable degree. Conclusion: The combined administration of CR and TQ exerted the most potent protection against APAP-induced nephrotoxicity through its anti-inflammatory and free radical-scavenging effects (antioxidant) which were comparable to that of NAC-treatment.
Language	English
Publishing date	2023-08-22
Publishing country	Saudi Arabia
Document type	Journal Article
ZDB-ID	1378024-4
ISSN	1319-0164
ISSN	1319-0164
DOI	10.1016/j.jsps.2023.101752
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Article: Nano-Resveratrol: A Promising Candidate for the Treatment of Renal Toxicity Induced by Doxorubicin in Rats Through Modulation of Beclin-1 and mTOR.

Alhusaini, Ahlam M / Fadda, Laila M / Alanazi, Abeer M / Sarawi, Wedad S / Alomar, Hatun A / Ali, Hanaa M / Hasan, Iman H / Ali, Rehab Ahmed

Frontiers in pharmacology

2022 Volume 13, Page(s) 826908

Abstract: Background: ...

Abstract	Background:
Language	English
Publishing date	2022-02-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2587355-6
ISSN	1663-9812
ISSN	1663-9812
DOI	10.3389/fphar.2022.826908
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Article: Resveratrol-Based Liposomes Improve Cardiac Remodeling Induced by Isoproterenol Partially by Modulating MEF2, Cytochrome C and S100A1 Expression.

Alhusaini, Ahlam M / Alghibiwi, Hanan K / Sarawi, Wedad S / Alsaab, Juman S / Alshehri, Samiyah M / Alqahtani, Qamraa H / Alshanwani, Aliah R / Aljassas, Ebtesam A / Alsultan, Ebtesam N / Hasan, Iman H

Dose-response : a publication of International Hormesis Society

2024 Volume 22, Issue 2, Page(s) 15593258241247980

Abstract: Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO ... ...

Abstract	Isoproterenol (ISO), a chemically synthesized catecholamine, belongs to β-adrenoceptor agonist used to treat bradycardia. The β-adrenergic agonist is an essential regulator of myocardial metabolism and contractility; however, excessive exposure to ISO can initiate oxidative stress and inflammation. This study aims to investigate the molecular mechanisms underlying ISO-induced cardiac remodeling, the protective efficacy of resveratrol (RSVR), and its liposomal formulation (L-RSVR) against such cardiac change. Wistar albino rats were evenly divided into 4 groups. Control group, ISO group received ISO (50 mg/kg, s.c.) twice a week for 2 weeks, and RSVR- and L-RSVR-treated groups in which rats received either RSVR or L-RSVR (20 mg/kg/day, p.o.) along with ISO for 2 weeks. ISO caused a significant elevation of the expression levels of BAX and MEF2 mRNA, S100A1 and cytochrome C proteins, as well as DNA fragmentation in cardiac tissue compared to the control group. Treatment with either RSVR or L-RSVR for 14 days significantly ameliorated the damage induced by ISO, as evidenced by the improvement of all measured parameters. The present study shows that L-RSVR provides better cardio-protection against ISO-induced cardiac injury in rats, most likely through modulation of cardiac S100A1 protein expression and inhibition of inflammation and apoptosis.
Language	English
Publishing date	2024-04-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2440820-7
ISSN	1559-3258
ISSN	1559-3258
DOI	10.1177/15593258241247980
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Article ; Online: The Association between Cardiovascular Risk Factors and Carotid Intima-Media Thickness in 42,726 Adults in UK Biobank: A Cross-Sectional Study.

AlGhibiwi, Hanan K / Sarawi, Wedad S / Alosaimi, Manal E / Alhusaini, Ahlam M / Assiri, Mohammed A / Algarzae, Norah K

Journal of cardiovascular development and disease

2023 Volume 10, Issue 9

Abstract: ... from lowest to highest. The lowest cIMT quartile was defined as having a mean cIMT < 588 µm, while the highest ... cIMT quartile was defined as having a mean cIMT > 748 µm. Specifically, the highest cIMT quantile group ...

Abstract	Background: Traditional modifiable cardiovascular risk factors, such as high blood pressure, have long been positively correlated with high carotid intima-media thickness (cIMT). However, traditional cardiovascular risk factors made a minor contribution to cIMT variance, meaning that other markers may be regarded as independent markers for increasing cIMT. Aims: To investigate the simple demographic patterns of carotid intima-media thickness (cIMT) in the UK Biobank and to identify which upstream cardiovascular disease (CVD) risk factors are independently associated with cIMT. Methods and results: A cross-sectional-based study of healthy middle-aged people recruited in the UK between 2006 and 2010 ( Results: This study showed that the cardiovascular risk profile generally worsened across the cIMT quantiles from lowest to highest. The lowest cIMT quartile was defined as having a mean cIMT < 588 µm, while the highest cIMT quartile was defined as having a mean cIMT > 748 µm. Specifically, the highest cIMT quantile group had a worse CVD risk factors profile compared to the lowest cIMT quantile group. It was found that, for every one SD increase in age and systolic blood pressure, the mean cIMT increased by 0.357 SD and 0.115 SD, respectively. Conclusion: Systolic blood pressure and age were the strongest independent risk factors for a high cIMT value compared to other risk factors.
Language	English
Publishing date	2023-08-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2777082-5
ISSN	2308-3425 ; 2308-3425
ISSN (online)	2308-3425
ISSN	2308-3425
DOI	10.3390/jcdd10090358
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Article ; Online: The implication of LPS/TLR4 and FXR receptors in hepatoprotective efficacy of indole-3-acetic acid and chenodeoxycholic acid.

Aljarboa, Amjad S / Alhusaini, Ahlam M / Sarawi, Wedad S / Mohammed, Raeesa / Ali, Rehab A / Hasan, Iman H

Life sciences

2023 Volume 334, Page(s) 122182

Abstract: Aim: Valproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), ... ...

Abstract	Aim: Valproic acid (VPA) belongs to the first-generation antiepileptic drugs, yet its prolonged use can cause life-threatening liver damage. The importance of our study is to investigate the protective effect of indole-3-acetic acid (IAA), chenodeoxycholic acid (CDCA) and their combination on VPA-induced liver injury focusing on lipopolysaccharides (LPS)/toll-like receptor 4 (TLR4) pathway and farnesoid X receptor (FXR). Methods: Thirty rats were randomly assigned into five groups, normal control group, VPA group received 500 mg/kg of VPA intraperitoneally. The remaining groups were orally treated with either 40 mg/kg of IAA, 90 mg/kg of CDCA, or a combination of both, along with VPA. All treatments were administered one hour after the administration of VPA for three weeks. Key findings: VPA group showed significant elevations in the liver weight/body weight ratio, serum aminotransferases, triglyceride, and total cholesterol levels. Hepatic glutathione (GSH) level and superoxide dismutase (SOD) activity were significantly decreased, while malondialdehyde (MDA) level, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), lipopolysaccharide (LPS) and caspase 3 were significantly increased. Likewise, immunohistochemical analysis revealed that TLR4 expression was elevated, whereas FXR expression was downregulated in hepatocytes. IAA substantially ameliorated all previously altered parameters, whereas CDCA treatment showed a partial improvement compared to IAA. Surprisingly, combination therapy of IAA with CDCA showed an additive effect only in the hepatic expression of TLR4 and FXR proteins. Significance: IAA could be a promising protective agent against VPA-induced liver injury.
MeSH term(s)	Rats ; Animals ; Lipopolysaccharides/pharmacology ; Chenodeoxycholic Acid/pharmacology ; Chenodeoxycholic Acid/metabolism ; Toll-Like Receptor 4/metabolism ; Chemical and Drug Induced Liver Injury, Chronic/metabolism ; Liver/metabolism ; Glutathione/metabolism
Chemical Substances	Lipopolysaccharides ; Chenodeoxycholic Acid (0GEI24LG0J) ; Toll-Like Receptor 4 ; indoleacetic acid (6U1S09C61L) ; Glutathione (GAN16C9B8O)
Language	English
Publishing date	2023-10-18
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	3378-9
ISSN	1879-0631 ; 0024-3205
ISSN (online)	1879-0631
ISSN	0024-3205
DOI	10.1016/j.lfs.2023.122182
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Article ; Online: Roles of Nrf2/HO-1 and ICAM-1 in the Protective Effect of Nano-Curcumin against Copper-Induced Lung Injury

Wedad S. Sarawi / Ahlam M. Alhusaini / Hanan K. Alghibiwi / Juman S. Alsaab / Iman H. Hasan

International Journal of Molecular Sciences, Vol 24, Iss 13975, p

2023 Volume 13975

Abstract	Copper (Cu) is an essential trace element for maintaining normal homeostasis in living organisms. Yet, an elevated level of Cu beyond homeostatic capacity may lead to oxidative damage of cellular components in several organs, including the lungs. This work investigated the effects of curcumin (Curc) and nano-curcumin (nCurc) against Cu-induced lung injury, accenting the roles of oxidative stress, inflammation, and the nuclear factor erythroid 2-related factor/heme oxygenase-1 Nrf2/HO-1 pathway. Rats were challenged with 100 mg/kg of copper sulfate (CuSO 4 ) while being treated with Curc or nCurc for 7 days. Cu-triggered lung oxidative stress detected as dysregulation of oxidative/antioxidant markers, a downregulation of Nrf-2/HO-1 signaling, and an increase in the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and intracellular adhesion molecule-1 (ICAM-1). Additionally, it decreased the expression of lung-specific proteins, surfactant protein-C (SP-C), and mucin-1 (MUC-1), induced apoptosis, and caused changes in lung histology. Curc and nCurc alleviated CuSO 4 -induced lung injury by suppressing oxidative damage and inflammation and activating Nrf-2/HO-1. They also prevented apoptosis and restored the normal expression of SP-C and MUC-1. We concluded that nCurc exhibited superior efficacy compared with Curc in mitigating CuSO 4 -induced lung injury. This was associated with reduced oxidative stress, inflammation, and apoptotic responses and increased Nrf2/HO-1 signaling and expression of SP-C and MUC-1.
Keywords	curcumin ; lung toxicity ; inflammation ; copper sulfate ; oxidative stress ; Nrf2/HO-1 pathway ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	610 ; 500
Language	English
Publishing date	2023-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: L-Ascorbic Acid and Curcumin Prevents Brain Damage Induced via Lead Acetate in Rats: Possible Mechanisms.

Alhusaini, Ahlam Mohamed / Fadda, Laila M / Alsharafi, Huda / Alshamary, Amjad Fahad / Hasan, Iman H

Developmental neuroscience

2021 Volume 44, Issue 2, Page(s) 59–66

Abstract: Lead acetate (lead ac.) is a widespread ecological toxicant that can cause marked neurotoxicity and decline in brain functions. This study aimed to evaluate the possible neuroprotective role of L-ascorbic acid (ASCR) and curcumin (CRCM) alone or together ...

Abstract	Lead acetate (lead ac.) is a widespread ecological toxicant that can cause marked neurotoxicity and decline in brain functions. This study aimed to evaluate the possible neuroprotective role of L-ascorbic acid (ASCR) and curcumin (CRCM) alone or together against lead ac.-induced neurotoxicity. Rats were injected with lead ac. then treated orally with ASCR and CRCM alone or in combination for 7 days. Lead ac. caused elevation in brain tumor necrosis factor-α, interleukin-6, caspase-3, and malondialdehyde levels, while superoxide dismutase, reduced glutathione as well as the expression of brain-derived neurotrophic factor, cAMP response element-binding, and Beclin1 were downregulated. Expressions of C/EBP homologous protein and mammalian Target of rapamycin kinase were upregulated in brain tissues matched with the control group. Histopathological examination supported the previously mentioned parameters, the administration of the antioxidants in question modulated all the altered previous parameters. The combination regimen achieved the superlative results in the antagonizing lead ac.-induced neurotoxicity via its antioxidant and antiapoptotic activities.
MeSH term(s)	Animals ; Ascorbic Acid/metabolism ; Ascorbic Acid/pharmacology ; Brain ; Curcumin/metabolism ; Curcumin/pharmacology ; Mammals ; Organometallic Compounds/metabolism ; Organometallic Compounds/toxicity ; Oxidative Stress ; Rats
Chemical Substances	Organometallic Compounds ; Curcumin (IT942ZTH98) ; Ascorbic Acid (PQ6CK8PD0R) ; lead acetate (RX077P88RY)
Language	English
Publishing date	2021-12-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	556887-0
ISSN	1421-9859 ; 0378-5866
ISSN (online)	1421-9859
ISSN	0378-5866
DOI	10.1159/000521619
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