Thymoquinone nanoparticles protect against cisplatin-induced nephrotoxicity in Ehrlich carcinoma model without compromising cisplatin anti-cancer efficacy

Harkaeh, Steve; Qari, Yousef; Tashkandi, Hanaa; Almuhayawi, Mohammed S.; Saber, Saber H.; Aljahdali, Emad; El-Shitany, Nagla A.; Shaker, Soad; Lucas, Filipa Ribeiro; Alamri, Turki; Al-Jaouni, Soad; Mousa, Shaker A.

doi:10.1016/j.jksus.2021.101675

Cited by 15 publications

(12 citation statements)

References 42 publications

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“…The antioxidant bene ts of these supplements were probably quite comparable to one another. The liver bene ts from exposure to all of these pure antioxidant chemicals because they enhance the liver's antioxidant defence system, lowering its production of reactive oxygen species and raising the production of antioxidant enzymes (Iraz et al, 2006, Kart et al, 2010, Thangapandiyan et al, 2019, Khedr et al, 2020, Harkaeh et al, 2022, Xue et al, 2022. Across all these studies, the researchers concluded that omega-3 positive effects might be related to the compound's antioxidant properties.…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Omega-3 Fatty Acids Against Cisplatin Induced Hepatocellular Damage and Oxidative Stress in Rats

ALRAMADNEH,

Abu-Harirah,

Saleh

et al. 2023

Preprint

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Cisplatin has a high rate of effectiveness in treating cancer, its use is restricted due to the severe adverse consequences it produces. Nephrotoxicity, neurotoxicity, and ototoxicity are only a few of the unwanted side effects. In the case of cisplatin, hepatotoxicity is thought to be caused by oxidative stress brought on by an increase in reactive oxygen species (ROS). Omega-3 is an antioxidant that reduces the production of reactive oxygen species by inhibiting the enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. This study aimed to compare the beneficial effects of omega-3 therapy against the harmful effects of cisplatin-induced hepatotoxicity and to determine the effect of cisplatin on hepatic pro-oxidant or antioxidant systems. The rats were divided into four groups (n = 6 per group) and treated with single dosages of cisplatin (5 milligrams per kilogram) and omega-3 (20 milligrams per kilogram over fourteen days by intraperitoneal administration), or cisplatin combined with omega-3. In addition, the rat’s blood was tested for alkaline phosphatase, aspartate transaminase, and alanine transaminase levels. We observed higher levels of lipid peroxidation products, total oxidant status, and ALT in the cisplatin group compared to the control group. Conversely, it was revealed that glutathione peroxidase and superoxide dismutase levels were considerably lower in the cisplatin group compared to the control group. Omega-3 has significantly reduced the toxicity of cisplatin in the liver. Our biochemical results confirmed our histological observations of central venous dilations, pericenter and periportal sinusoidal dilations, parenchymal inflammation, vacuolar abnormalities in hepatocytes, biliary duct proliferation, and caspase-3 positive hepatocytes. In conclusion, Omega-3 can provide biochemical and histological protection against cisplatin-induced hepatotoxicity.

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Section: Discussionmentioning

confidence: 99%

Protective Effects of Omega-3 Fatty Acids Against Cisplatin Induced Hepatocellular Damage and Oxidative Stress in Rats

ALRAMADNEH,

Abu-Harirah,

Saleh

et al. 2023

Preprint

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“…The previous studies had shown that the encapsulation of thymoquinone (THY), as a potent antioxidant and anti-inflammatory compound, into PLGA and polyvinyl alcohol (PVA) polymers, and then using pluronic 127, as a non-anionic surfactant, could improve the poor solubility of THY and increase its bioavailability [ 99 ]. In this regard, the co-treatment of PLGA nanoparticle encapsulating THY (NP THY) with cisplatin can reduce cisplatin-induced nephrotoxicity in Ehrlich solid carcinoma (ESC) mice model without losing antitumor properties of cisplatin [ 100 ]. Kidney damage markers (i.e., uric acid, urea, creatinine, and cystatin c) were decreased in the treated mice in comparison with the cisplatin group.…”

Section: Polymeric Nano-formulationsmentioning

confidence: 99%

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011–2022 review

et al. 2022

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Cisplatin (CDDP) is a well-known platinum-based drug used in the treatment of various malignancies. However, the widespread side effects that this drug leaves on normal tissues make its use limited. Since cisplatin is mainly eliminated from the kidneys, CDDP-induced nephrotoxicity is the most significant dose-limiting complication attributed to cisplatin, which often leads to dose withdrawal. Considering the high efficiency of cisplatin in chemotherapy, finding renoprotective drug delivery systems for this drug is a necessity. In this regard, we can take advantages of different nanoparticle-based approaches to deliver cisplatin into tumors either using passive targeting or using specific receptors. In an effort to find more effective cisplatin-based nano-drugs with less nephrotoxic effect, the current 2011–2022 review study was conducted to investigate some of the nanotechnology-based methods that have successfully been able to mitigate CDDP-induced nephrotoxicity. Accordingly, although cisplatin can cause renal failures through inducing mitochondria dysfunction, oxidative stress, lipid peroxidation and endoplasmic reticulum stress, some CDDP-based nano-carriers have been able to reverse a wide range of these advert effects. Based on the obtained results, it was found that the use of different metallic and polymeric nanoparticles can help renal cells to strengthen their antioxidant systems and stay alive through reducing CDDP-induced ROS generation, inhibiting apoptosis-related pathways and maintaining the integrity of the mitochondrial membrane. For example, nanocurcumin could inhibit oxidative stress and acting as a ROS scavenger. CONPs could reduce lipid peroxidation and pro-inflammatory cytokines. CDDP-loaded silver nanoparticles (AgNPs) could inhibit mitochondria-mediated apoptosis. In addition, tea polyphenol-functionalized SeNPs (Se@TE) NPs could mitigate the increased level of dephosphorylated AKT, phosphorylated p38 MAPK and phosphorylated c-Jun N-terminal kinase (JNK) induced by cisplatin. Moreover, exosomes mitigated cisplatin-induced renal damage through inhibiting Bcl2 and increasing Bim, Bid, Bax, cleaved caspase-9, and cleaved caspase-3. Hence, nanoparticle-based techniques are promising drug delivery systems for cisplatin so that some of them, such as lipoplatins and nanocurcumins, have even reached phases 1–3 trials.

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“…Nanotechnology is a promising approach to improving the biopharmaceutical performance of low bioavailable, bioactive molecules of plant origin [ 112 ]. The therapeutic efficacy of TQ encapsulated inside various nanoformulation systems (illustrated in Figure 5 ) as nano-TQ resulted in a significant increase in intended pharmacological activity compared to the conventional TQ formulation system [ 113 ].…”

Section: Nanotechnology-mediated Bone-specific Delivery Of Ns And/or ...mentioning

confidence: 99%

Utilization of Nanotechnology to Improve Bone Health in Osteoporosis Exploiting Nigella sativa and Its Active Constituent Thymoquinone

et al. 2022

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Osteoporosis, a chronic bone disorder, is one of the leading causes of fracture and morbidity risk. Numerous medicinally important herbs have been evaluated for their efficacy in improving bone mass density in exhaustive preclinical and limited clinical studies. Nigella sativa L. has been used as local folk medicine, and traditional healers have used it to manage various ailments. Its reported beneficial effects include controlling bone and joint diseases. The present manuscript aimed to provide a sound discussion on the pharmacological evidence of N. sativa and its active constituent, thymoquinone, for its utility in the effective management of osteoporosis. N. sativa is reported to possess anti-IL-1 and anti-TNF-α-mediated anti-inflammatory effects, leading to positive effects on bone turnover markers, such as alkaline phosphatase and tartrate-resistant acid phosphatase. It is reported to stimulate bone regeneration by prompting osteoblast proliferation, ossification, and decreasing osteoclast cells. Thymoquinone from N. sativa has exhibited an antioxidant effect on bone tissue by reducing the FeNTA-induced oxidative stress. The present manuscript highlights phytochemistry, pharmacological effect, and the important mechanistic perspective of N. sativa and its active constituents for the management of osteoporosis. Further, it also provides sound discussion on the utilization of a nanotechnology-mediated drug delivery approach as a promising strategy to improve the therapeutic performance of N. sativa and its active constituent, thymoquinone, in the effective management of osteoporosis.

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Thymoquinone nanoparticles protect against cisplatin-induced nephrotoxicity in Ehrlich carcinoma model without compromising cisplatin anti-cancer efficacy

Cited by 15 publications

References 42 publications

Protective Effects of Omega-3 Fatty Acids Against Cisplatin Induced Hepatocellular Damage and Oxidative Stress in Rats

Protective Effects of Omega-3 Fatty Acids Against Cisplatin Induced Hepatocellular Damage and Oxidative Stress in Rats

Ameliorative impacts of polymeric and metallic nanoparticles on cisplatin-induced nephrotoxicity: a 2011–2022 review

Utilization of Nanotechnology to Improve Bone Health in Osteoporosis Exploiting Nigella sativa and Its Active Constituent Thymoquinone

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