Nephrotoxicity is described as the usually occurred kidney hassle that is due to any drug or toxin. A wide range of therapeutic agents can adversely affect the kidney which result in acute kidney injury, kidney infection and nephritic syndrome because of increase in number of potent therapeutic drugs like antibiotics, chemotherapeutic agents and Non-steroidal anti-inflammatory agents. Nephroprotective agents are those substances which shows preventive activity against nephrotoxicity. The medicinal plants have protective properties due to the presence of various chemical substances. A phytotherapeutic or phytomedicine approach to modern drug development can provide many promising drugs from traditional medicinal plants. Various plants and polyherbal formulations are used for the treatment of kidney diseases. The extracts of natural products and antioxidants present in plants have been reported to show protective effects against nephrotoxicity. This presentation will help you to understand herbal drugs which show the potent nephroprotective effect due their antioxidant, diuretic, anti-inflammatory, antispasmodic properties.

1. HERBALS AS NEPHROPROTECTIVE
AGENTS
By : Shivani A. Shelke
From : F.Y.M.Pharmacy (Quality Assurance)
Under the guidance of : Mr. Keyur Shastri (Assistant Professor)
V.E.S. College Of Pharmacy , Chembur
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2. Contents
● Introduction to kidney and its functions
● Nephron
● Diseases related to kidney
● Nephrotoxicity in detail
● Agents causing nephrotoxicity
● Different nephrotoxicity mechanism
● Prevalence
● Plants as nephroprotective agents
● Potential of natural products as nephroprotective agents
● Marketed preparations
● Case study
● Conclusion
● References
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3. Introduction To Kidney
1. Two bean shaped organs located on
either side of the spine in
retroperitoneal space.
2. Weight : 125 to 175 gms in males
115 to 155 gms in females.
1. Size : 10 to 12 cm long , 5 to 7 cm
wide , 3 cm thick.
2. Functional unit of kidney is
Nephron.
3. There are about 1 million nephron
in each kidney.
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4. 4

5. ● Held together by connective
tissue.
● Each nephron made of a
glomerulus and renal tubule.
● Glomerulus is filtration site in
cortex
● Tubules form Loop of Henle ,
extending a few centimeters in
medulla.
● Reabsorption and secretion
takes place in tubules.
NEPHRON
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6. Diseases related to kidney
● Nephrotoxicity (occurs when body is exposed to a drug or
toxin).
● When kidney damage occurs , body unable to rid of excess
urine and wastes from body and blood electrolytes (such as
Potassium & Magnesium ) will all become elevated.
● Most of the therapeutic agents can adversely affect kidney
resulting in acute renal failure , renal cysts , kidney injury ,
chronic interstitial nephritis and nephritic syndrome.
● Renal failure primarily denotes failure of the excretory
function of kidney , leading to retention of nitrogenous waste
products of metabolism in the blood.
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7. 7

8. Nephrotoxicity
● Poisonous effect of some substances, both toxic chemicals and
medication (nephrotoxins are chemicals displaying nephrotoxicity)
on the kidneys.
● Occurs when kidney-specific detoxification and excretion do not
work properly due to the damage or destruction of kidney function
by exogenous or endogenous toxicants.
● A number of antibiotics including the penicillins, cephalosporins,
tetracyclines, as well as aminoglycosides and sulfonamides, are
potential nephrotoxins.
● Exposure to chemical reagents like ethylene glycol, carbon
tetrachloride, sodium oxalate and heavy metals such as lead,
mercury, cadmium and arsenic also induces nephrotoxicity.
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9. AGENTS CAUSING NEPHROTOXICITY
Drugs, diagnostic agents and chemicals are well know to be nephrotoxic.
The following are some of the important nephrotoxic agents.
A) Heavy metals :- Mercury, Arsenic, Lead, Bismuth
B) Antineoplastic agents :-
● Alkylating agents :- Cisplatin, Cyclophosphamide
● Nitrosoureas :- Streptozotocin, Carmustine, Lomustine, & Semustine
● Antimetabolites :- High dose Methotrexate, Cytosine Arabinose, High
dose 6-thioguanine, 5-fluorouracil
● Antitumor antibiotics :- Mitomycin, Mithramycin, Doxorubicin
● Biologic agents :- Recombinant leukocyte and interferon
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10. C) Antimicrobial agents :- Tetracycline, Acyclovir, Pentamidine,
Sulphadiazine, Trimethoprim, Rifampicin, Amphotericin B
D) Aminoglycosides :- Streptomycin, Gentamicin, Amikacin, Kanamycin
E) Miscellaneous
Radiocontrast agents :- Non-steroidal anti-inflammatory agents (NSAID’s):
Ibuprofen, Indomethacin, Aspirin etc.
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11. DIFFERENT NEPHROTOXICITY MECHANISM
1.Gentamicin induced toxicity
● Aminoglycoside, widely used in treatment of gram-negative bacterial
infections.
● Not absorbed in the small intestine so is not active when given orally.
It is administered by IV, IM or topical route.
● However there nephrotoxicity and ototoxicity are the major limitations
in clinical use.
● It generally causes drug induced dose dependent Nephrotoxicity in 10
to 20% of therapeutic courses.
● Characterized by direct tubular necrosis, without morphological
changes in glomerular structure.
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12. 12

13. 2.Cisplatin Toxicity
● It is a highly effective antineoplastic DNA alkylating agent used
against a wide variety of cancers.
● It decreases antioxidants and antioxidant enzymes leading to
enhanced generation of reactive oxygen metabolites and lipid
peroxidation.
● An early report indicated that nephrotoxicity might occur in as many
as 50 to 75% of patients receiving this drug.
● The clinical use of cisplatin is often complicated by nephrotoxicity,
ototoxicity, gastrointestinal disturbances like nausea, vomiting and
myelosuppression.
● Primary targets of cisplatin - proximal straight and distal convoluted
tubules where it accumulates and promotes cellular damage, by
multiple mechanisms including oxidative stress, DNA damage and
apoptosis.
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14. 14

15. ● Also known as paracetamol. It is a widely used analgesic and
antipyretic drug that is safely employed for a wider range of
treatments.
● Renal insufficiency occurs in approximately 1-2% of patients with
acetaminophen overdose.
● Overdose of acetaminophen in humans is fairly common and is often
associated with hepatic and renal damage.
● The toxicity results in renal tubular damage and acute renal failure
even lead to death in humans and experimental animals.
3.Acetaminophen induced toxicity
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16. 16

17. PREVALENCE
● 10% of the population worldwide is affected by chronic kidney
disease (CKD), and millions die each year because they do not
have access to affordable treatment.
● The Global Burden of Disease (GBD) 2015 study estimated that,
in 2015, 1.2 million people died from kidney failure, an increase
of 32% since 2005.
● Between 2005 and 2015, the prevalence of diabetic kidney
disease increased by 39.5% globally.
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18. Plants as nephroprotective agents
● Nephroprotective agents are the substances which possess
protective activity against nephrotoxicity.
● Medicinal plants have curative properties due to the presence
of various complex chemical substances.
● Ancient literature has prescribed various herbs for the cure of
kidney disease.
● Co-administration of various medicinal plants possessing
nephroprotective activity along with different nephrotoxic
agents may attenuate(reduce) its toxicity.
● Certain plants which are documented in literature for their
nephroprotective effects are described further.
18

19. POTENTIAL OF NATURAL PRODUCTS AS
NEPHROPROTECTIVE AGENTS
1. PANAX GINSENG
1. BUPLEURUM FALCATUM
1. AERVA LANATA
1. LEPIDIUM SATIVUM
1. OCIMUM SANCTUM
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20. PANAX GINSENG
● B.S : Chemical constituents obtained from roots of plant Panax
Ginseng.
● FAMILY : ARALIACEAE
● STRUCTURE :
GINSENOSIDE Rg3 20

21. MECHANISM OF ACTION
● The antioxidant potential of Ginsenoside Rg3 is used in the
treatment of Cisplatin Induced Nephrotoxicity.
❖ Herbal marketed preparations : HIVITAL , NATURE’s
TRUTH
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22. BUPLEURUM FALCATUM
● B.S : Chemical constituents obtained from roots of the plant
● FAMILY : APIACEAE
● STRUCTURE :
SAIKOSAPONIN-d
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23. MECHANISM OF ACTION
● Saikosaponin-d led to decline of reactive oxygen species(ROS)
and specific ROS scavenger N-acetyl cysteine and stopped the
Gentamicin Induced Nephrotoxicity.
❖ Herbal marketed preparations : KAWAII PHARM ,
NUTRITION CARE
23

24. AERVA LANATA
● B.S : Also called Gorakhaganja, Chaya .
Chemical constituents obtained from entire
plant.
● FAMILY : Amaranthaceae
● STRUCTURE :
24

25. MECHANISM OF ACTION
● The ethanol extract of Aerva lanata possesses marked
nephroprotective activity with minimal toxicity and could offer a
promising role in the treatment of acute renal failure caused by
nephrotoxins like cisplatin & gentamicin.
● Herbal marketed preparations : Ceylon herbal , bixa botanica
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26. LEPIDIUM SATIVUM
● B.S. : Also called Garden cress. Chemical constituents from
seeds of plant Lepidium Sativum.
● Family : Brassicaceae.
● Structure :
Quercetin
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27. MECHANISM OF ACTION
● The n-butanol extract of the seeds possesses good antioxidant
activity which is used in the treatment of cisplatin induced
nephrotoxicity.
❖ Herbal marketed preparation : Nutrissence
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28. OCIMUM SANCTUM
● B.S. : Also called Tulsi. Chemical constituents obtained from the
leaves of Ocimum Sanctum.
● Family : Lamiaceae.
● Structure :
EUGENOL
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29. MECHANISM OF ACTION
● Leaves are reported to have Eugenol (71%) whose antioxidant
property helps in relieving Gentamicin Induced Nephrotoxicity.
❖ Herbal marketed preparations : Herbal Hills , Healthvit Tul-C
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30. HERBAL MARKETED PREPARATIONS
● Altace® Tablets - King Pharmaceuticals, US
● Toprol® Tablets - Lopressor
● Ketoadd® Tablets - Sun Pharmaceuticals Ltd
● Gokshura and Shuddha guggulu Tablets - Sri Sri Tattva
● Kurki Capsules - Organic India LKC
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31. 31

32. CASE STUDY
NEPHROPROTECTIVE EFFECT OF HERBAL
EXTRACT EURYCOMA LONGIFOLIA ON
PARACETAMOL INDUCED NEPHROTOXICITY IN
RATS
● The aim of present study was to evaluate the protective effect of the
herbal extract Eurycoma Longifolia (EL) against Paracetamol-induced
(PCM) nephrotoxicity in rat model.
● 40 Wistar rats were randomly divided into 5 groups of 8 rats each.
● 5 groups : 1. Control (Vehicle 10 ml/kg daily for 14 days) 2.PCM
alone (Vehicle 10 ml/kg + Intraperitoneal(IP) injection of PCM 200
mg/kg daily) 3. EL 100 ( EL 100 mg/kg + IP injection of PCM 200
mg/kg) 4. EL 200 ( EL 200 mg/kg + IP injection of PCM 200 mg/kg)
5. EL 400 ( EL 400 mg/kg + IP injection of PCM 200 mg/kg). 32

33. ● The body weight of the animals was recorded on 0 , day 7 and day 14
of the treatment.
● After 14 days , serum was obtained for the measurement of protein ,
albumin and creatinine levels.
● The 24 hr urine sample was collected from day 14 to day 15 for
estimation of creatinine levels.
● On day 15 , the animals were sacrificed and subjected to necroscopy.
● The kidney samples were dissected , trimmed of connective tissues
and washed with normal saline to eliminate blood contamination.
● The samples were allowed to clot and centrifuged at 3000 rpm at 30℃
for 15 min and the separated serum was used for biochemical
estimations.
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34. RESULTS :
1. Effect of EL treatment on body weight
Body weight (g)
CONTROL PCM alone EL 100 EL 200 EL 400
DAY 0 136.5 ± 12.54 136.5 ± 07.94 145.3 ± 03.91 137.4 ± 09.63 145.0 ± 03.62
DAY 7 141.6 ± 19.29 135.8 ± 12.94 138.1 ± 04.73 131.9 ± 17.01 139.6 ± 13.14
DAY 14 154.1 ± 23.76 149.3 ± 17.21 146.1 ± 03.87 142.0 ± 16.58 156.0 ± 11.49
There were no significant changes in the body weight of rats
in all treatment groups in comparison to PCM alone group.
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35. ● Decrease in level of total protein & albumin in rats of PCM alone group as compared to
control.
● Increase in level of serum urea & creatinine in PCM alone group as compared to control.
● Decrease in level of total protein & albumin in EL 200 & EL 400 as compared to control.
● Decrease in level of serum urea & creatinine in EL 200 & EL 400 as compared to control.
● Decrease in creatinine clearance in PCM alone group as compared to control.
● Increase in creatinine clearance in EL 200 & EL 400 as compared to control.
2. Effect of serum and urine biochemistry
Experimental group
CONTROL PCM alone EL 100 EL 200 EL 400
Serum total protein 11.1 ± 2.0 7.0 ± 1.2 8.9 ± 1.6 9.4 ± 1.4 10.1 ± 1.6
Serum albumin 3.6 ± 0.7 1.7 ± 0.7 1.6 ± 0.8 3.1 ± 0.8 3.1 ± 0.3
Blood urea 18.0 ± 0.1 41.7 ± 7.3 42.8 ± 7.5 21.7 ± 3.4 18.0 ± 2.3
Serum creatinine 0.8 ± 0.1 1.6 ± 0.5 1.7 ± 0.3 0.9 ± 0.1 0.8 ± 1.6
Albumin clearance 0.86 ± 0.13 0.31 ± 0.12 0.30 ± 0.05 0.61 ± 0.22 0.87 ± 0.26
Creatinine ratio 22.8 25.1 24.8 24.4 23.7
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36. 3. Effect of EL treatment on kidney histopathology
● PCM alone group showed tubular
degeneration, damaged glomeruli,
epithelial degeneration.
● Animals treated with EL 100 mg/kg
showed moderate degenerative
changes in glomeruli and tubules.
● Animal treated with EL 200 mg/kg
showed significant nephroprotection
with minimal degenerative changes.
● High dose EL 400 mg/kg provided
highest protection with normal
appearance of glomeruli and
tubules.
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37. Result :
● The present study demonstrated dose-dependent nephroprotective
activity of Eurycoma Longifolia in a rat model of Paracetamol-induced
nephrotoxicity.
● Pretreatment with EL extract dose-dependently prevented kidney injury
as evidenced by serum and urine biochemical analysis and kidney
histopathology.
● Hence , EL is a potential nephroprotective agent against drug-induced
nephrotoxicity.
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38. CONCLUSION
● From this study, it is clear that the medicinal plants play a vital role
against on various diseases.
● A variety of medicinal plants and plants extracts have been reported
for its significant nephroprotective activity in animal models.
● The results of this study indicate that extracts of leaves and other plant
plants of some medicinal plants have good potentials for use in kidney
damage.
● This review study give evidential explore mechanism of action of
medicinal plants against experimentally induced nephrotoxicity.
● The nephroprotective activity is probably due to the presence of
Flavonoids in all the few medicinal plants.
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39. REFERENCES
1. Article, R. (2012). A REVIEW ON SOME NEPHROPROTECTIVE
MEDICINAL PLANTS Kanchan Gaikwad *, Pradeep Dagle , Pushpalata
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Bharati Vidyapeeth ’ s College of Pharmacy , CBD Belapur Navi Mumbai ,
Maharashtra , I. 3(08), 2451–2454.
2. Vaya, R. K., Sharma, A., Singhvi, I. J., & Agarwal, D. K. (2017).
Nephroprotective Plants: A Review. Journal of Bioscience And Technology,
8(1), 801–812.
3. Mohana Lakshmi, S., Kiran Reddy, U. T., & Sandhya Rani, K. S. (2012). A
review on medicinal plants for nephroprotective activity. Asian Journal of
Pharmaceutical and Clinical Research, 5(4), 8–14.
4. Pabla, N., & Dong, Z. (2008). Cisplatin nephrotoxicity: Mechanisms and
renoprotective strategies. Kidney International, 73(9), 994–1007.
39

40. 5. Balakumar, Pitchai et al. “Gentamicin-induced nephrotoxicity: Do we have a
promising therapeutic approach to blunt it?” Pharmacological research 623
(2010): 179-86 .
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https://doi.org/10.1155/2019/4916519

42. THANKYOU !!!
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